Lumpectomy Lounge....let's talk!

Galiano

Hi - I'm not sure if this is the forum I should be posting in or maybe the June surgery group? I had a major duct excision almost two weeks and have so many questions - I should probably try splitting them up into different topics, but maybe others here have shared experiences? I was diagnosed with ADH and multiple papillomas with necrosis. The surgeon is sending the pathology slides for another opinion on margins and to rule out DCIS but the waiting for results (again) is hard. I lost all the feeling in the side of the excision and the skin over the nipple is really raw and bleeding again (I had to start putting gauze back in the surgical bra). Has anyone else had this happen or have any suggestions for creams/moisturizes? I posted a similar question in the 6 month club topic, but might be more appropriate here? They also found a tumor on my thyroid that's TI-RADS 4 - I'm sure it's just coincidence, but I can't help worrying - back for more appointments tomorrow. I'm nearing the end of the recovery period (which is great, and I'm really relieved that it just came back with ADH), but I'm overwhelmed with the idea of going back to work. Sorry for the rambling post... and thanks for listening. I hope everyone's procedures and recoveries go well!

RobinLT

I have been debating if I should share my current status. But this group has been a lifeline for me and I always appreciate the support that is given to any and all decisions and outcomes.

I just passed my 2 yr mark after my lumpectomy and radiation therapy. Six months ago, I stopped taking any meds for my BC. Anastrozole slowly but surely led me to a severe mental fog that tipped into the deep end. I was totally untethered mentally. Short term memory was almost non-existent. I got lost driving my usual route, was unable to perform my job, and I was about to slip into Alzheimer’s or dementia.

My oncologist agreed it was as due to the rx. After just 3 weeks off, I was back, baby!

We tried tamoxifen. One month in and I was on the old slippery slope of cognitive dysfunction again. My oncologist supports my decision to be drug free. And I feel oddly at peace with my decision and my future. I will continue to monitor, of course. I’m curious if this is experience is very rare , or just not talked about much.

edj3

RobinLT I'm very thankful for you and the others who DO share what you've experienced. That helps me so much as I navigate my own course here. I'm just about to finish radiation, and my MO wants me on tamoxifen. I'm deeply, deeply reluctant to take it for a whole host of reasons but am also looking to make a good, balanced decision. So I truly appreciate you sharing.

pontiacpeggy

RobinLT, I have one friend who is on this site, who also experienced the type of cognitive problems you did while taking anastrozole. She switched to Letrozole as I recall and they cleared up right away.

I wonder, and have no clue if this is true, if the lack of estrogen might play a part. Or the way the AI works - perhaps slightly differently on each of us. So many unknowns for a drug that is so important.

HUGS!

DeeBB

This is the cream my Radiation Oncologist suggested I get and it did wonders through and after my radiation. I would recommend it to anyone. I ordered it off Amazon.

Oronine H Ointment

Darcys-mom

I am glad you wrote about your experiences. Alzheimer's and Dementia symptoms are my biggest worries. My mother had Alzheimer's for 18 years and I would take Breast Cancer over that any day.

chisandy

Robin, not surprised you can forgo the hormone therapy—tumor <1 cm, and only Grade 1, the BCS5 online calculator would likely put you at low risk for recurrence even w/o it. (You look great, BTW).

Galiano, go to the baby-care aisle of the pharmacy and get some nursing pads—much less irritating than gauze. (Or look for nonstick gauze pads, which have a perforated plastic coating over the gauze to make for a smoother surface). Good luck on the thyroid biopsy.

movingsoccermom

Hello Robin. I too was completely unable to take the AI's. The last straw for me was exceptional dizziness and days long headaches that would not respond to treatment, and this after 14 days. Even with my recurrence I would not have changed my decision. My consulting oncologist feels that I was likely stage 4 de novo, but there wasn't a PET scan done at that time. For me, life is for living which meant no AI's. My Mom had a stroke, so no Tamoxifen either. Shrug.

I hope you have a better course! All the best.

Stellawt57

What a world wind these past months have been, getting used to the changes in my body, mind and self confidence. I met with my PS in May and we created my corrective/revision surgery and scheduled it for July 12th. Now there could be a wrench thrown in the plan. I had my first colonoscopy two weeks ago with an excessive number of polyps being found (grrr). Those sent for biopsy were not cancerous (yah), but I was referred to a genetic counselor. I met with her the other morning and we are doing genetic testing for BRCA 1& 2, CHEK2, and ATM/PALB2 for mutations. I'm also having the genes Attenuated APC and Lynch Syndrome checked for colon, pancreatic, and other cancers. The link is on my dad's side of the family. He had advanced colorectal cancer which took him quickly. We lost my mom at age 48 and her mother passed in her mid 60's (in the early 80's). This was prior to mammography being part of women's routine health care. The counselor has requested the lab complete the analysis by July 10th so I can continue with my planned surgery or cancel and have discussions with my BS & PS for a mastectomy/implants if there is a mutation. I asked my BS early on if my cancer was genetic form. She felt sure that it was not because of my high estrogen and progesterone numbers along with several other risk markers. I've always had the question "is it genetics" in the back of my mind and now I will have a definitive answer. I really need to know for my children and grandchildren (a daughter who has a daughter and son and my son). This disease is not something I want to pass on to them, but knowing will help them create preventative health care plans. I know I'm getting ahead of myself as the results could be negative, but I'm concerned. I see my Integrative Dr. later today for an acupuncture session which I need to help manage my anxiety. I always appreciate the support and help I receive from all!

movingsoccermom

Hello Stella. While I hope that you find answers, it is possible you will not. My family is rife with cancer on both sides. My Sister, my Mom and 3/6 of her sisters had breast cancer. One sister had ovarian cancer, another had uterine cancer. My Dad and 1/2 sisters died of colon cancer. I had genetic testing done 4 years ago with my initial diagnosis and no mutations were found. I still find that unbelievable, but suspect they just have not yet identified what the mutation is, although we suspect it is a gene that fails to prevent mutations, thus allowing cancer to develop. I had hoped to avoid breast cancer by nursing my kiddos (27 months total), but alas that did not work. I have told my daughter to get a baseline mammogram at 40, since all our breast cancers started after the age of 45. Of all the breast cancers, mine is the only one to metastasize. Darn the luck.

Good luck!!

edj3

Chiming in on the we may never get the answers we're looking for.

On my mothers' side I have a very strong history of blood cancers (my mother, her sister, and her sister's twin who's already died from it). And my maternal grandmother died from colon cancer. I myself have been diagnosed w/ melanoma and now breast cancer.

I have zero known gene mutations for any cancer. As my husband says, I'm an overachiever.

Sgold1023

Hi. I had existing silicone implants prior to diagnosis. I will have a lumpectomy on my left breast as my tumor is only 6mm and then radiation. I have 6 yo silicone implants. I was going to downsize my implants and I may still. THe PS seemed wary of doing that and then doing radiation but the radiation oncologist felt okay about doing it. The PS seemed to also feel why have implants at all, just do fat transfer and avoid any potential complication. I am unsure what to do. I am nearly 51 and am wondering if I took them out altoghether if I would regret it as it will be a drastic reduction.

mjb1018

Sgold1023. I'll be 51 in October. Have had my saline implants over 15 years...I've lost track! Anyway, I had lumpectomy then radiation with implants in place. I consulted about removing them first, but PS and RO said no problem to radiate with them in place. I'm glad I kept them! I'm a year out from radiation now. The treated breast is higher, smaller (with a dent) and tighter. I consulted with a PS about 6 months ago wanting to do implant exchange. She explained how radiation permanently damages the tissue and going in could be like waking a sleeping lion. She referred me to a specialist for microsurgery (using my own tissue) and he said I don't have enough. 😳 A blessing and a curse! We discussed waiting the full year, which is where I am now. My capsular contracture has worsened. I want to get it fixed because it's painful. Other than the dent, I actually like the shape and position. However, I don't want to lift/reduce the non treated side. I'd rather place a slightly larger implant but don't know if i can get the treated side to match. At any rate, radiated tissue does present more challenges in terms of implants. Complications are much more likely, which is why using our own tissue is preferred

mjb1018

P. S. After all that, my suggestion is to wait until you’re done with radiation. The treated breast will most likely change. I’d worry about downsizing now, then having to revise again.

Sgold1023

mjb1018:

Thank you, that is helpful. I thought everything was pretty simple and straightforward until I talked to the PS. Not that it is his fault, I think I threw him for a loop when I said I wanted to remove my implants and do something smaller.

Galiano

thank you ChiSandy for the advice! The pads help. I'm waiting for genetic test results now. The skin is finally healing but I've developed hard painful lumps around two of the remaining ducts. I'm assuming this is just part of the residual inflammation and will go away eventually. It's hard not to worry about every little thing.

mysticalcity

RobinLT my cryoablation doctor just gave me some estimated percentages of recurrence for my particular tumor type. I was suprised to see that 5 years of anti-estrogen therapy only reduced my 10 year recurrence estimate by 3%. So based on your side effects (and even for myself I have to think about long term bone density and cardiac impact) I fully get your wanting to discontinue the meds. One thing you might want to look at is natural ways and natural supplements that would reduce your estrogen levels as a substitute. Here is an link to a biophysicist who has done a lot of excellent work in that area: https://www.biohackerslab.com/ep51-dr-anthony-jay/

And there are some newer things that will also be coming out it appears: https://medicalxpress.com/news/2018-03-breast-cancer-drug-human-clinical.html

https://www.ttconcology.com/

mysticalcity

also, just reposting an earlier post from this site by marijen that I had saved with a lot of natural anti-estrogen remedies. Very long, but well worth the read:

Sep 13, 2017 03:06AM - edited Sep 13, 2017 03:09AM by marijen

Natural Therapies

Protecting Breast Cells Against Dangerous Estrogens

The stronger form of estrogen, estradiol, can be converted into the weaker form, estriol, in the body without using drugs. Estriol is considered to be a more desirable form of estrogen. It is less active than estradiol, so when it occupies the estrogen receptor, it blocks estradiol's strong "growth" signals. Using a natural substance the conversion of estradiol to estriol increased by 50% in 12 healthy people (Michnovicz et al. 1991). Furthermore, in female mice prone to developing breast cancer the natural substance reduced the incidence of cancer and the number of tumors significantly. The natural substance was indole-3-carbinol (I3C).

Indole-3-carbinol (I3C) is a phytochemical isolated from cruciferous vegetables (broccoli, cauliflower, Brussels sprouts, turnips, kale, green cabbage, mustard seed, etc.). I3C given to 17 men and women for 2 months reduced the levels of strong estrogen, and increased the levels of weak estrogen. But more importantly, the level of an estrogen metabolite associated with breast and endometrial cancer, 16--a-hydroxyestrone, was reduced by I3C (Bradlow et al. 1991).

When I3C changes "strong" estrogen to "weak" estrogen, the growth of human cancer cells is inhibited by 54-61% (Telang et al. 1997). Moreover, I3C provoked cancer cells to self-destruct (kill themselves via apoptosis). Induction of cell death is an approach to suppress carcinogenesis and is the prime goal of cytotoxic chemotherapy. The increase in apoptosis induced by I3C before initiation of new tumor development may contribute to suppression of tumor progression. Nontoxic I3C can reliably facilitate apoptosis (12 week treatment in rats); thus, this phytonutrient may become a standard adjunct in the treatment of breast cancer (Zhang et al. 2003)

I3C inhibits human breast cancer cells (MCF7) from growing by as much as 90% in culture; growth arrest does not depend on estrogen receptors (Cover et al. 1998). Furthermore, I3C induces apoptosis in tumorigenic (cancerous) but not in nontumorigenic (non-cancerous) breast epithelial cells (Rahman et al. 2003).

I3C does more than just turn strong estrogen to weak estrogen. 16-a-Hydroxyestrone (16-OHE) and 2-hydroxyestrone (2-OHE) are metabolites of estrogen in addition to estriol and estradiol. 2-OHE is biologically inactive, while 16-OHE is biologically active; that is, like estradiol, it can send "growth" signals. In breast cancer, the dangerous 16-OHE is often elevated, while the protective 2-OHE is decreased. Cancer-causing chemicals change the metabolism of estrogen so that 16-OHE is elevated. Studies show that people who take I3C have beneficial increases in the "weak" estriol form of estrogen and also increases in protective 2-OHE.

African-American women who consumed I3C, 400 mg for 5 days, experienced an increase in the "good" 2-OHE and a decrease of the "bad" 16-OHE. However, it was found that the minority of women who did not demonstrate an increase in 2-OHE, had a mutation in a gene that helps metabolize estrogen to the 2-OHE version. Those women had an eight times higher risk of breast cancer (Telang et al. 1997).

I3C Stops Cancer Cells from Growing

Tamoxifen is a drug prescribed to reduce breast cancer metastases and improve survival. I3C has modes of action similar to tamoxifen. I3C inhibited the growth of estrogen-receptor-positive breast cancer cells by 90% compared to 60% for tamoxifen. The mode of action attributed to I3C's impressive effect was interfering with the cancer cell growth cycle. Adding tamoxifen to I3C gave a 5% boost (95% total inhibition) (Cover et al. 1999).

In estrogen-receptor-negative cells, I3C stopped the synthesis of DNA by about 50%, whereas tamoxifen had no significant effect. I3C also restored p21 and other proteins that act as checkpoints during the synthesis of a new cell. Tamoxifen showed no effect on p21. Restoration of these growth regulators is extremely important. For example, tumor suppressor p53 works through p21 that I3C restores. I3C also inhibits cancers caused by chemicals. If animals are fed I3C before exposure to cancer-causing chemicals, DNA damage and cancer are virtually eliminated (Cover et al. 1999).

A study on rodents shows that damaged DNA in breast cells is reduced 91% by I3C. Similar results are seen in the liver (Devanaboyina et al. 1997). Female smokers taking 400 mg of I3C significantly reduced their levels of a major lung carcinogen. Cigarette chemicals are known to adversely affect estrogen metabolism (Taioli et al. 1997).

There is no proven way to prevent breast cancer, but the best and most comprehensive scientific evidence so far supports phytochemicals such as I3C (Meng et al. 2000). The results from a placebo-controlled, double-blind dose-ranging chemoprevention study on 60 women at increased risk for breast cancer demonstrated that I3C at a minimum effective dosage 300 mg per day is a promising agent for breast cancer prevention (Wong et al. 1997). The results of a single-blind phase I trial which studied the effectiveness of I3C in preventing breast cancer in nonsmoking women who are at high risk of breast cancer are awaited. The rationale for this study is that I3C, ingested twice daily, may be effective at preventing breast cancer.

I3C was found to be superior to 80 other compounds, including tamoxifen, for anticancer potential. Indoles, which down-regulate estrogen receptors, have been proposed as promising agents in the treatment and prevention of cancer and autoimmune diseases such as multiple sclerosis, arthritis, and lupus. Replacement of all the chemically altered estrogen drugs, such as tamoxifen, with a new generation of chemically altered indole drugs that fit in the aryl-hydrocarbon (Ah) receptor and regulate estrogen indirectly may prove beneficial to cancer patients (Bitonti et al. 1999). An I3C tetrameric derivative (chemically derived) is currently a novel lead inhibitor of breast cancer cell growth, considered a new, promising therapeutic agent for both ER+ and ER- breast cancer (Brandi et al. 2003).

A summary of studies shows that indole-3-carbinol (I3C) can:

• Increase the conversion of estradiol to the safer estriol by 50% in healthy people in just 1 week (Michnovicz et al. 1991)
• Prevent the formation of the estrogen metabolite, 16,alpha-hydroxyestrone, that prompts breast cancer cells to grow (Chen et al. 1996), in both men and women in 2 months (Michnovicz et al. 1997)
• Stop human cancer cells from growing (54-61%) and provoke the cells to self-destruct (apoptosis) (Telang et al. 1997)
• Inhibit human breast cancer cells (MCF7) from growing by as much as 90% in vitro (Ricci et al. 1999)
• Inhibit the growth of estrogen-receptor-positive breast cancer cells by 90%, compared to tamoxifen's 60%, by stopping the cell cycle (Cover et al. 1999)
• Prevent chemically induced breast cancer in rodents by 70-96%. Prevent other types of cancer, including aflatoxin-induced liver cancer, leukemia, and colon cancer (Grubbs et al. 1995)
• Inhibit free radicals, particularly those that cause the oxidation of fat (Shertzer et al. 1988)
• Stop the synthesis of DNA by about 50% in estrogen-receptor-negative cells, whereas tamoxifen had no significant effect (Cover et al. 1998)
• Restore p21 and other proteins that act as checkpoints during the synthesis of a new cancer cell. Tamoxifen has no effect on p21 (Cover et al. 1998)
• Virtually eliminate DNA damage and cancer prior to exposure to cancer-causing chemicals (in animals fed I3C) (Grubbs et al. 1995)
• Reduce DNA damage in breast cells by 91% (Devanaboyina et al. 1997)
• Reduce levels of a major nitrosamine carcinogen in female smokers (Taioli et al. 1997)

How to Use I3C

While the evidence is compelling, it is too soon to know exactly how effective I3C will be as an adjuvant breast cancer therapy (see the Breast Cancer References for citations pertaining specifically to I3C).

Suggested dosage: Take one 200-mg capsule of I3C twice a day, for those under 120 pounds. For those who weigh more than 120 pounds, three 200-mg capsules a day are suggested. Women who weigh over 180 pounds should take four 200-mg I3C capsules a day.

Caution: Pregnant women should not take I3C because of its modulation of estrogen. I3C appears to act both at the ovarian and hypothalamic levels, whereas tamoxifen appears to act only on the hypothalamic-pituitary axis as an anti-estrogen. Both I3C and tamoxifen block ovulation by altering preovulatory concentrations of luteinizing hormone (LH) and follicle stimulating hormone (FSH) (Gao et al. 2002). The reported aversion to cruciferous vegetables by pregnant women may be associated with their ability to change estrogen metabolism. Estrogen is a necessary growth factor for the fetus.

Apigenin

Apigenin, a flavone (ie, a class of flavonoids) that is present in fruits and vegetables (eg, onions, oranges, tea, celery, artichoke, and parsley), has been shown to possess anti-inflammatory, antioxidant, and anticancer properties. Many studies have confirmed the cancer chemopreventive effects of apigenin (Patel 2007).

Apigenin stimulates apoptosis in breast cancer cells (Chen 2007). A 2012 study showed that apigenin slowed the progression of human breast cancer by inducing cell death, inhibiting cell proliferation, and reducing expression of a gene associated with cancer growth (Her2/neu). In another study, it was noted that blood vessels responsible for feeding cancer cells were smaller in apigenin-treated mice compared to untreated mice. This is significant because smaller vessels mean restricted nutrient flow to the tumors and may have served to starve the cancer as well as limit its ability to spread (Mafuvadze 2012).

Apigenin has been proven to have a synergistic treatment effect when combined with the chemotherapy drug paclitaxel (Xu 2011). In a study, apigenin increased the efficacy of the chemotherapy drug 5-Fluorouracil against breast cancer cells (Choi 2009).

Astragalus

Astragalus, an herb used for centuries in Asia, has exhibited immune-stimulatory effects. Astragalus potentiates lymphokine-activated killer cells (Chu 1988). One study found that astragalus could partially restore depressed immune function in tumor-bearing mice (Cho 2007a), while another concluded that "…astragalus could exhibit anti-tumor effects, which might be achieved through activating the…anti-tumor immune mechanism of the host" (Cho 2007b).

It was observed in a clinical trial that astragalus inhibited the proliferation of breast cancer cells. Authors of the study stated, "The antiproliferation mechanisms may be related to its effects of up-regulating the expressions of p53…" (Ye 2011). Similar findings were noted in a previous experiment (Deng 2009).

Blueberry

Blueberries are rich in anthocyanins (ie, dark pigments in fruits) and pterostilbenes (ie, antioxidant closely related to resveratrol). The anti-cancer effects of blueberries are mediated by multiple mechanisms:

Blueberry extracts block DNA damage. Damage to cellular DNA underlies most forms of cancer. By preventing such damage, blueberry extracts can block the malignant transformation of healthy cells (Aiyer 2008).

Blueberry extracts inhibit angiogenesis. Rapidly-growing cancers recruit new blood vessels to meet their ravenous appetites for nutrients and oxygen. Blueberry inhibits new tumor blood vessel growth, known as angiogenesis (Gordillo 2009; Liu 2011).

Blueberry extracts trigger cancer cells' suicide. If normal cells replicate too fast, they are programmed to die through apoptosis. Cancerous cells, by contrast, ignore that programming, constantly doubling their population unchecked. Blueberry components restore normal programming and induce apoptosis in cells from a variety of cancers, putting the brakes on their rapid growth (Katsube 2003; Yi 2005; Seeram 2006; Srivastava 2007; Alosi 2010).

Blueberry extracts stop excessive proliferation. Uncontrolled cell reproduction results in formation of dangerous tumors, as cells ignore the normal signals to stop growing. By restoring normal cellular signaling, blueberry extracts stop such out-of-control proliferation (Yi 2005; Adams 2010; Nguyen 2010). In an experimental breast cancer cell line, blueberry significantly reduced breast cancer cell proliferation, leading the researchers to state that "blueberry anthocyanins … demonstrated anticancer properties by inhibiting cancer cell proliferation and by acting as cell antiinvasive factors and chemoinhibitors" (Faria 2010). In rats with experimentally induced breast cancer, the volume of new breast tumor formation was reduced by 40% in the group of rats supplemented with blueberry compared to the control group (Srinivasan 2008).

Blueberry extracts slow tumor spread by invasion and metastasis. Solid cancers produce matrix metalloproteinases, which are "protein-melting" enzymes that help them invade adjacent tissues and that enable them to metastasize. Blueberry extracts block matrix metalloproteinases, thereby inhibiting cancer invasion and metastasis (Adams 2010a; Matchett 2005). In one experiment published in 2011, blueberry extract was administered to mice with breast cancer. Compared to the control group, tumor volume was 75% lower in mice fed blueberry extract. Moreover, mice fed blueberry extract developed 70% fewer liver metastases and 25% fewer lymph node metastases compared to the control group (Adams 2011).

Chrysin

Breast cancers that are estrogen-receptor positive can grow and be exacerbated in the presence of estrogen in the body. One aim of drug therapy for estrogen-receptor positive breast cancer is to decrease the levels of estrogen in the body. To that end, drugs used to block the enzyme (ie, aromatase) that converts testosterone into estrogen (ie, aromatase inhibitors) are widely used in women with estrogen-receptor positive breast cancer. Chrysin, a flavonoid, is a natural aromatase inhibitor (Campbell 1993; Mohammed 2011).

Coffee

Coffee, especially brews enriched with chlorogenic acid, protect cells against the DNA damage that leads to aging and cancer development (Bakuradze 2011; Hoelzl 2010; Misik 2010). Growing tumors develop the ability to invade local and regional tissue by increasing their production of "protein-melting" enzymes called matrix metalloproteinases. Chlorogenic acid—present in coffee—strongly inhibited matrix metalloproteinase activity (Jin 2005; Belkaid 2006).

A 2011 study reported that postmenopausal women who drank 5 cups of coffee dailyexhibited a 57% decreased risk of developing estrogen-receptor negative (non-hormone-responsive) breast cancer (Li 2011). Chlorogenic acid and other polyphenols are the likely beneficial agents in such cancers (Bageman 2008).

Curcumin

Curcumin is extracted from the spice turmeric and is responsible for the orange/yellow pigment that gives the spice its unique color. Turmeric is a perennial herb of the ginger family and a major component of curry powder. Chinese and Indian people, both in herbal medicine and in food preparation, have safely used it for centuries.

Curcumin has a number of biological effects in the body. However, one of the most important functions is curcumin's ability to inhibit growth signals emitted by tumor cells that elicit angiogenesis (growth and development of new blood vessels into the tumor).

Curcumin inhibits the epidermal growth factor receptor and is up to 90% effective in a dose-dependent manner. It is important to note that while curcumin has been shown to be up to 90% effective in inhibiting the expression of the epidermal growth factor receptor on cancer cell membranes, this does not mean it will be effective in 90% of cancer patients or reduce tumor volume by 90%. However, because two-thirds of all cancers overexpress the epidermal growth factor receptor and such overexpression frequently fuels the metastatic spread of the cancer throughout the body, suppression of this receptor is desirable.

Other anticancer mechanisms of curcumin include:

• Inhibition of the induction of basic fibroblast growth factor (bFGF). bFGF is both a potent growth signal (mitogen) for many cancers and an important signaling factor in angiogenesis (Arbiser et al. 1998).
• Antioxidant activity. In vitro it has been shown to be stronger than vitamin E in prevention of lipid peroxidation (Sharma 1976; Toda et al. 1985).
• Inhibition of the expression of COX-2 (cyclooxygenase 2), the enzyme involved in the production of prostaglandin E2 (PGE-2), a tumor-promoting hormone-like agent (Zhang et al. 1999).
• Inhibition of a transcription factor in cancer cells known as nuclear factor-kappa B (NF-KB). Many cancers overexpress NF-KB and use this as a growth vehicle to escape regulatory control (Bierhaus et al. 1997; Plummer et al. 1999).
• Increased expression of nuclear p53 protein in human basal cell carcinomas, hepatomas, and leukemia cell lines. This increases apoptosis (cell death) (Jee et al. 1998).
• Increases production of transforming growth factor-beta (TGF-beta), a potent growth inhibitor, producing apoptosis (Park et al. 2003; Sporn et al. 1989).
• TGF-beta is known to enhance wound healing and may play an important role in the enhancement of wound healing by curcumin (Mani H et al. 2002; Sidhu et al. 1998).
• Inhibits PTK (protein tyrosine kinases) and PKC (protein kinase C). PTK and PKC both help relay chemical signals through the cell. Abnormally high levels of these substances are often required for cancer cell signal transduction messages. These include proliferation, cell migration, metastasis, angiogenesis, avoidance of apoptosis, and differentiation (Reddy et al. 1994; Davidson et al. 1996).
• Inhibits AP-1 (activator protein-1) through a non-antioxidant pathway. While curcumin is an antioxidant (Kuo et al. 1996), it appears to inhibit signal-transduction via protein phosphorylation thereby decreasing cancer-cell activity, regulation, and proliferation (Huang et al. 1991).

Based on the favorable, multiple mechanisms listed above, higher-dose curcumin would appear to be useful for cancer patients to take. However, as far as curcumin being taken at the same time as chemotherapy drugs, there are contradictions in the scientific literature. Therefore, caution is advised. Please refer to the Cancer Chemotherapy protocol before considering combining curcumin with chemotherapy.

Curcumin's effects are a dose dependent response, and a standardized product is essential. The recommended dose is four 900-mg capsules 3 times per day, preferably with food.

*Green Tea (green tea extract can cause liver failure)

As a tumor grows it elicits new capillary growth (angiogenesis) from the surrounding normal tissues and diverts blood supply and nutrients away from the tissue to feed itself. Unregulated tumor angiogenesis can facilitate the growth of cancer throughout the body. Antiangiogenesis agents, including green tea, inhibit this new tumor blood vessel (capillary) growth.

Green tea contains epigallocatechin gallate EGCG, a polyphenol that helps to block the induction of vascular endothelial growth factor (VEGF). Scientists consider VEGF essential in the process of angiogenesis and tumor endothelial cell survival. It is the EGCG fraction of green tea that makes it a potentially effective adjunct therapy in the treatment of breast cancer. In vivo studies have shown green tea extracts to have the following actions on human cancer cells (Jung et al. 2001b; Muraoka et al. 2002):

• Inhibition of tumor growth by 58%
• Inhibition of activation of nuclear factor-kappa beta
• Inhibition of microvessel density by 30%
• Inhibition of tumor-cell proliferation in vitro by 27%
• Increased tumor-cell apoptosis 1.9-fold
• Increased tumor endothelial-cell apoptosis threefold

The most current research shows that green tea may have a beneficial effect in treating cancer. While drinking green tea is a well-documented method of preventing cancer, it is difficult for the cancer patient to obtain a sufficient quantity of EGCG anticancer components in that form. Standardized green tea extract is more useful then green tea itself because the dose of EGCG can be precisely monitored and greater doses can be ingested without excessive intake of liquids. A suggested dose for a person with breast cancer is 5 capsules of 350-mg lightly caffeinated green tea extract 3 times a day with each meal. Each capsule should provide at least 100 mg of EGCG. It may be desirable to take a decaffeinated version of green tea extract in the evening to ensure that the caffeine does not interfere with sleep. Those sensitive to caffeine may also use this decaffeinated form.

However, there are benefits to obtaining some caffeine. Studies show that caffeine potentiates the anticancer effects of tea polyphenols, including the critical EGCG. Caffeine will be discussed in further detail later in this protocol. Green tea extract is available in a decaffeinated form for those sensitive to caffeine or those who want to take the less-stimulating decaffeinated green tea extract capsules for their evening dose.

Conjugated Linoleic Acid (CLA)

Conjugated linoleic acid (CLA) found naturally, as a component of beef and milk, refers to isomers of octadecadienoic acid with conjugated double bonds. CLA is essential for the transport of dietary fat into cells, where it is used to build muscle and produce energy. CLA is incorporated into the neutral lipids of mammary fat (adipocyte) cells, where it serves as a local reservoir of CLA. It has been proposed that CLA may be an excellent candidate for prevention of breast cancer (Ip et al. 2003). Low levels of CLA are found in breast cancer patients but these do not influence survival. Nevertheless, it has been hypothesized that a higher intake of CLA might have a protective effect on the risk of metastasis (Chajes et al. 2003).

CLA was shown to prevent mammary cancer in rats if given before the onset of puberty. CLA ingested during the time of the "promotion" phase of cancer development conferred substantial protection from further development of breast cancer in the rats by inducing cell kill of pre-cancerous lesions (Ip et al. 1999b). It was determined that feeding CLA to female rats while they were young and still developing conferred life-long protection against breast cancer. This preventative action was achieved by adding enough CLA to equal 0.8% of the animal's total diet (Ip et al. 1999a).

CLA inhibits the proliferation of human breast cancer cells (MCF-7), induced by estradiol and insulin (but not EGF). In fact, CLA caused cell kill (cytotoxicity) when tumor cells were induced with insulin (Chujo et al. 2003). The antiproliferative effects of CLA are partly due to their ability to elicit a p53 response that leads to growth arrest (Kemp et al. 2003). CLA elicits cell killing effects in human breast tumor cells through both p53-dependent and p53 independent pathways according to the cell type (Majumder et al. 2002). Refer to Cancer Treatment The Critical Factors, for more information on determining the p53 status of cancer. The effects of CLA are mediated by both direct action (on the epithelium) as well as indirect action through the stroma.

The growth suppressing effect of CLA may be partly due to changes in arachidonic distribution among cellular lipids and an altered prostaglandin profile (Miller et al. 2001). Intracellular lipids may become more susceptible to oxidative stress to the point of producing a cytotoxic effect (Devery et al. 2001). CLA has the ability to suppress arachidonic acid. Since arachidonic acid can produce inflammatory compounds that can promote cancer proliferation, this may be yet another explanation for CLA's anticancer effects.

Life Extension's recommendation for CLA is a dose of 3000-4000 mg daily, which is approximately 1% of the average human diet. The suggested amount required to obtain the overall cancer-preventing effects is only 3000-4000 mg daily in divided doses.

CLA may work via a mechanism similar to that of antidiabetic drugs not only by enhancing insulin-sensitivity but also by increasing plasma adiponectin levels, alleviating hyperinsulinemia (Nagao et al. 2003) protecting against cancer. A number of human cancer cell lines express the PPAR-gamma transcription factor, and agonists for PPAR-gamma can promote apoptosis in these cell lines and impede their clonal expansion both in vitro and in vivo. CLA can activate PPAR-gamma in rat adipocytes, possibly explaining CLA's antidiabetic effects in Zucker fatty rats. A portion of CLA's broad-spectrum anticarcinogenic activity is probably mediated by PPARgamma activation in susceptible tumor (McCarty 2000). However, CLA's anticarcinogenic effects could not be confirmed in one epidemiologic study in humans (Voorips et al. 2002). (Note: The term PPAR-gamma is an acronym for peroxisome proliferator-activatedreceptor-gamma. A PPAR-gamma agonist such as Avandia®, Actos®, or CLA activates the PPAR-gamma receptor. This class of drug is being investigated as a potential adjuvant therapy against certain types of cancer.)

Caffeine

Caffeine occurs naturally in green tea and has been shown to potentiate the anticancer effects of tea polyphenols. Caffeine is a model radio-sensitizing agent that is thought to work by abolishing the radiation-induced G2-phase checkpoint in the cell cycle. Caffeine can induce apoptosis of a human lung carcinoma cell line by itself and it can act synergistically with radiation to induce tumor cell kill and cell growth arrest. The cancer cell killing effect of caffeine is dependent on the dose (Qi et al. 2002).

Caffeine enhances the tumor cell killing effects of anticancer drugs and radiation. A preliminary report on radiochemotherapy combined with caffeine for high-grade soft tissue sarcomas in 17 patients, (treated with cisplatin, caffeine, and doxorubicin after radiation therapy) determined complete response in six patients, partial response in six and no change in five patients. The effectiveness rate of caffeine-potentiated radiochemotherapy was therefore 17%, and contributed to a satisfactory local response and the success of function-saving surgery for high-grade soft tissue sarcomas (Tsuchiya et al. 2000).

In a randomized, double blind placebo-controlled crossover study, the effects of caffeine as an adjuvant to morphine in advanced cancer patients was found to benefit the cognitive performance and reduce pain intensity (Mercadante et al. 2001).

Cancer patients should note that one study demonstrated that caffeine reduced the cytotoxic effect of paclitaxel on human lung adenocarcinoma cell lines (Kitamoto et al. 2003).

To ascertain the inhibitory effects of caffeine, mice at high risk of developing malignant and nonmalignant tumors (SKH-1), received oral caffeine as their sole source of drinking fluid for 18-23 weeks. Results revealed that caffeine inhibited the formation and decreased the size of both nonmalignant tumors and malignant tumors (Lou et al. 1999).

In cancer cells, p53 gene mutations are the most common alterations observed (50-60%) and are a factor in both carcinomas and sarcomas. Caffeine has been shown to potentiate the destruction of p53-defective cells by inhibiting p53's growth signal. The effects of this are to inhibit and override the DNA damage-checkpoint and thus kill dividing cells. Caffeine uncouples cell-cycle progression by interfering with the replication and repair of DNA(Sakurai et al. 1999; Ribeiro et al. 1999; Jiang et al. 2000; Valenzuela et al. 2000).

Caffeine inhibits the development of Ehrlich ascites carcinoma in female mice (Mukhopadhyay 2001). Topical application of caffeine inhibits the occurrence of cancer and increases tumor cell death in radiation-induced skin tumors in mice (Lu et al. 2002). Caffeine inhibits solid tumor development and lung experimental metastasis induced by melanoma cells (Gude et al. 2001).

Consumption of coffee, tea, and caffeine was not associated with breast cancer incidence in a study of 59,036 Swedish women (aged 40-76 years) (Michels et al. 2002).

Lignans

Lignans are found in high concentrations in flaxseed and sesame. Once consumed, lignans are converted in the intestines into enterolactone.Enterolactone has been shown to inhibit angiogenesis and promote cancer cell apoptosis (Bergman 2007; Chen 2007).

Enterolactone inhibits the aromatase enzyme, which converts testosterone into estrogen (Brooks 2005; Wang 1994).

Researchers conducted an analysis of breast cancer risk and dietary lignan intake in 3158 women. They determined that premenopausal women with the highest lignan intake had a 44% reduced risk of developing breast cancer (McCann 2004).

Thirty-two women awaiting surgery for breast cancer were randomized to receive either a muffin containing 25 grams of flaxseeds or no flaxseed (control group). Post-operative analysis of the cancerous tissue revealed that markers of tumor growth were reduced by 30-71% in the flaxseed group versus no reduction in the control group (Thompson 2005). Scientists concluded that "dietary flaxseed has the potential to reduce tumor growth in patients with breast cancer."

In order to examine the relationship between dietary lignan intake and breast cancer, researchers assessed the diets of 1122 women in the 1-2 years before breast cancer diagnosis. They noted that postmenopausal women with the highest dietary intake of lignans had a 71% decreased risk of death from breast cancer (McCann 2010).

Melatonin

One of the most important supplements for a breast cancer patient is the hormone melatonin. Melatonin inhibits human breast cancer cell growth (Cos et al. 2000) and reduces tumor spread and invasiveness in vitro (Cos et al.1998). Indeed, it has been suggested that melatonin acts as a naturally occurring anti-estrogen on tumor cells, as it down-regulates hormones responsible for the growth of hormone-dependent mammary tumors (Torres-Farfan 2003).

A high percentage of women with estrogen-receptor-positive breast cancer have low plasma melatonin levels (Brzezinski et al. 1997). There have been some studies demonstrating changes in melatonin levels in breast cancer patients; specifically, women with breast cancer were found to have lower melatonin levels than women without breast cancer (Oosthuizen et al. 1989). Normally, women undergo a seasonal variation in the production of certain hormones, such as melatonin. However, it was found that women with breast cancer did not have a seasonal variation in melatonin levels, as did the healthy women (Holdaway et al. 1997).

Low levels of melatonin have been associated with breast cancer occurrence and development. Women who work predominantly at night and are exposed to light, which inhibits melatonin production and alters the circadian rhythm, have an increased risk of breast cancer development (Schernhammer et al. 2003). In contrast, higher melatonin levels have been found in blind and visually impaired people, along with correspondingly lower incidences of cancer compared to those with normal vision, thus suggesting a role for melatonin in the reduction of cancer incidence (Feychting et al. 1998).

Light at night, regardless of duration or intensity, inhibits melatonin secretion and phase-shifts the circadian clock, possibly altering the cell growth rate that is regulated by the circadian rhythm (Travlos et al. 2001). Disruption of circadian rhythm is commonly observed among breast cancer patients (Mormont et al. 1997; Roenneberg et al. 2002) and contributes to cancer development and tumor progression. The circadian rhythm alone is a statistically significant predictor of survival time for breast cancer patients (Sephton et al. 2000).

Melatonin differs from the classic anti-estrogens such as tamoxifen in that it does not seem to bind to the estrogen receptor or interfere with the binding of estradiol to its receptor (Sanchez-Barcelo 2003). Melatonin does not cause side effects, such as those) caused by the conventional anti-estrogen drug tamoxifen. Furthermore, when melatonin and tamoxifen are combined, synergistic benefits occur. Moreover, melatonin can increase the therapeutic efficacy of tamoxifen (Lissoni et al.1995) and biological therapies such as IL-2 (Lissoni et al. 1994).

How melatonin interferes with estrogen signaling is unknown, though recent studies suggest that it acts through a cyclic adenosine monophosphate (cAMP)-independent signaling pathway (Torres-Farfan 2003). It has been proposed that melatonin suppresses the epidermal growth factor receptor (EGF-R) (Blask et al. 2002) and exerts its growth inhibitory effects by inducing differentiation ("normalizing" cancer cells)(Cos et al. 1996). Melatonin directly inhibits breast cancer cell proliferation (Ram et al. 2000) and boosts the production of immune components, including natural killer cells (NK cells) that have an ability to kill metastasized cancer cells.

In tumorigenesis studies, melatonin reduced the incidence and growth rate of breast tumors and slowed breast cancer development (Subramanian et al. 1991). Furthermore, prolonged oral melatonin administration significantly reduced the development of existing mammary tumors in animals (Rao et al. 2000).

In vitro experiments carried out with the ER-positive human breast cancer cells (MCF-7 cells), demonstrated that melatonin, at a physiological concentration (1 nM) and in the presence of serum or estradiol (a) inhibits, in a reversible way, cell proliferation, (b) increases the expression of p53 and p21WAF1 proteins and modulates the length of the cell cycle, and (c) reduces the metastatic capacity of these cells and counteracts the stimulatory effect of estradiol on cell invasiveness. Further, this effect is mediated, at least in part, by a melatonin-induced increase in the expression of the cell surface adhesion proteins E-cadherin and beta (1)-integrin (Sanchez-Barcelo et al. 2003).

Melatonin can be safely taken for an indefinite period of time. The suggested dose of melatonin for breast cancer patients is 3-50 mg at bedtime. Initially, if melatonin is taken in large doses vivid dreams and morning drowsiness may occur. To avoid these minor side effects melatonin may be taken in low doses nightly and the dose slowly increased over a period of several weeks.

Pomegranate

Pomegranate, which is rich in antioxidants, has gained widespread popularity as a functional food (ie, has health benefits). The health benefits of the fruit, juice(s), and extract(s) have been studied in realtion to a variety of chornic diseases, including cancer (Syed 2012; Johanningsmeier 2011).

Researchers discovered that consumption of whole pomegranate seed oil and juice concentrate (Kim 2002) resulted in dramatic growth inhibition of estrogen-dependent breast cancer cells. The same study showed inhibition of tumor formation in rodent cells exposed to known breast carcinogens. Using different methods, another research group found a 42% reduction in tumor formation with whole pomegranate juice polyphenols and an 87% reduction with pomegranate seed oil (Mehta 2004).

Pomegranate seed oil is a potent inhibitor of aromatase, the enzyme that converts testosterone into estrogen (Adams 2010). This enzymatic blockade contributes to pomegranate seed oil's ability to inhibit growth of estrogen-dependent breast cancer cells. Pomegranate extract has also been shown to enhance the effects of the estrogen blocking drug tamoxifen, with the authors of a study stating that "…pomegranate combined with tamoxifen may represent a novel and a powerful approach to enhance and sensitize tamoxifen action" (Banerjee 2011). Pomegranate also increases apoptosis, even in cancer cells that lack estrogen receptors (Kim 2002).

Cancer cells need to grow new blood vessels to support their rapid growth and tissue invasion (angiogenesis). They typically do this by ramping up production of a variety of growth factors, including VEGF and inflammatory interleukins. Pomegranate seed oil powerfully inhibits production of VEGF while upregulating production of migratory inhibitory factor (MIF) in breast cancer cells. In a laboratory model of vessel growth, these modulations translated into a significant decrease in new blood vessel formation (Toi 2003). Pomegranate seed oil's capacity to block breast cancer development was also demonstrated in an organ culture model of mouse breast cancer (Mehta 2004).Treating the glands with pomegranate seed oil prior to exposure to a powerful carcinogen resulted in a 87% reduction in the number of cancerous lesions compared with controls.

Pomegranate seed oil contains a number of unique chemical constituents with potent biological effects. Punicic acid, an omega-5 polyunsaturated fatty acid that inhibits both estrogen-dependent and estrogen-independent breast cancer cell proliferation in lab cultures (Grossmann 2010), also induced apoptosis at rates up to 91% higher than those in untreated cell cultures—effects which appear to be related to fundamental regulation of cancer cell signaling pathways (Grossmann 2010).

PSK

PSK, which is a specially prepared polysaccharide extract from the mushroom Coriolus versicolor, has been studied extensively in Japan where it is used as a non-specific biological response modifier to enhance the immune system in cancer patients (Koda 2003; Noguchi 1995; Yokoe 1997). PSK suppresses tumor cell invasiveness by down-regulating several invasion-related factors (Zhang 2000). PSK has been shown to enhance NK cell activity in multiple studies (Ohwada 2006; Fisher 2002; Garcia-Lora 2001; Pedrinaci 1999).

In a study investigating the use of PSK in women with stage 2 breast cancer, post-operative participants received Tamoxifen with PSK (3 g daily) or Tamoxifen alone. The 5-year survival was 89.9% in the PSK group compared to 86.9% in the group receiving Tamoxifen only (Morimoto 1996).

Pterostilbene

Pterostilbene, a polyphenol found in blueberries, grapes, and in the bark of the Indian Kino Tree, is closely related to resveratrol (but with unique attributes). Pterostilbene's mechanisms of action include blocking enzymes that activate carcinogens (Mikstacka 2006, 2007), inducing apoptosis (Tolomeo 2005) and cell cycle arrest (Wang 2012), and enhancing nitric oxide-induced cell death (Ferrer 2007).

Researchers observed that pterostilbene markedly inhibited the growth of breast cancer cells in the laboratory by inducing apoptosis and cell cycle arrest (Wang 2012).

Quercetin

Quercetin is a flavonoid found in a broad range of foods, from grape skins and red onions to green tea and tomatoes. Quercetin's antioxidant and anti-inflammatory properties protect cellular DNA from cancer-inducing mutations (Aherne 1999). Quercetin traps developing cancer cells in the early phases of their replicative cycle, effectively preventing further malignant development and promoting cancer cell death (Yang 2006). Furthermore, quercetin favorably modulates chemical signaling pathways that are abnormal in cancer cells (Morrow 2001; Bach 2010).

In breast cancer cells, quercetin induces apoptosis and cell cycle arrest (Choi 2001; Chou 2010). Querctin inhibited the growth of tumors (Zhong 2003) and prolonged survival of mice with breast cancer (Du 2010).

Se-Methylselenocysteine

Se-methylselenocysteine (SeMSC), a naturally occurring organic selenium compound found to be an effective chemopreventive agent, is a new and better form of selenium. SeMSC is a selenoamino acid that is synthesized by plants such as garlic and broccoli. Methylselenocysteine (MSC) has been shown to be effective against mammary cell growth both in vivo and in vitro (Sinha et al. 1999) and has significant anticancer activity against mammary tumor development (Sinha et al. 1997). Moreover, Se-methylselenocysteine was one of the most effective selenium chemoprevention compounds and induced apoptosis in human leukemia cells (HL-60) in vitro (Jung et al. 2001a). Exposure to MSC blocks expansion of cancer colonies and premalignant lesions at an early stage by simultaneously modulating pathways responsible for inhibiting cell proliferation and enhancing apoptosis (Ip 2001).

Se-methylselenocysteine has been shown to:

• Produce a 33% better reduction of cancerous lesions than selenite.
• Produce a 50% decrease in tumor development.
• Induce cell death (apoptosis) in cancer cells.
• Inhibit cancer-cell growth (proliferation).
• Reduce density and development of tumor blood vessels.
• Down-regulate VEGF (vascular endothelial growth factor).

(Ip et al. 1992; Sinha et al. 1997; Sinha et al. 1999; Ip et al. 2001; Dong et al. 2001)

Unlike MSC, which is incorporated into protein in place of methionine, SeMSC is not incorporated into any protein, thereby offering a completely bioavailable compound. In animal studies, SeMSC has been shown to be 10 times less toxic than any other known form of selenium. Breast cancer patients may consider taking 400 mcg of SeSMC daily.

Sulforaphane

Sulforaphane, which is an isothiocyanate, is most highly concentrated in broccoli as well as in other cruciferous vegetables (eg, brussels sprouts, cabbage and cauliflower).

Sulforaphane detoxifies potential carcinogens, promotes apoptosis, blocks the cell cycle that is required for cancer cell replication, prevents tumor invasion into healthy tissue, enhances natural killer cell activity, and combats metastasis (Zhang 2007; Nian 2009; Traka 2008; Thejass 2006). Research has also demonstrated that sulforaphane is among the plant chemicals most potently capable of blocking the cancer-producing effects of ultraviolet radiation (Dinkova-Kostova 2008).

It has been observed that sulforaphane activated apoptosis (Pledgie-Tracy 2007) and inhibited the proliferation of breast cancer cells in culture (Ramirez 2009; Jo 2007). The binding of estrogen hormones to estrogen receptor alphapromotes breast cell proliferation, which can promote the progression of breast cancer. Researchers have also noted that sulforaphane down-regulates the expression of estrogen receptor alpha in breast cancer cells (Ramirez 2009).

In another clinical trial, mice injected with breast cancer cells developed 60% less tumor mass when treated with sulforaphane compared to untreated mice (Jackson 2004).

CoQ10

Coenzyme Q10 (CoQ10) is synthesized in humans from tyrosine through a cascade of eight aromatic precursors. These precursors require eight vitamins, which are vitamin C, B2, B3 (niacin) B6, B12, folic acid, pantothenic acid, and tetrahydrobiopterin as their coenzymes.

Since the 1960s, studies have shown that cancer patients often have decreased blood levels of coenzyme Q10 (Lockwood et al. 1995; Folkers 1996; Ren et al. 1997). In particular, breast cancer patients (with infiltrative ductal carcinoma) who underwent radical mastectomy were found to have significantly decreased tumor concentrations of CoQ10 compared to levels in normal surrounding tissues. Increased levels of reactive oxygen species may be involved in the consumption of CoQ10 (Portakal et al. 2000). These findings sparked interest in the compound as a potential anticancer agent (NCCAM 2002). Cellular and animal studies have found evidence that CoQ10 stimulates the immune system and can increase resistance to illness (Bliznakov et al. 1970; Hogenauer et al. 1981; NCCAM 2002).

CoQ10 may induce protective effect on breast tissue and has demonstrated promise in treating breast cancer. Although there are only a few studies, the safe nature of CoQ10 coupled with this promising research of its bioenergetic activity suggests that breast cancer patients should take 100 mg up to 3 times a day. It is important to take CoQ10 with some kind of oil, such as fish or flax, because dry powder CoQ10 is not readily absorbed.

In a clinical study, 32 patients were treated with CoQ10 (90 mg) in addition to other antioxidants and fatty acids; six of these patients showed partial tumor regression. In one of these cases the dose of CoQ10 was increased to 390 mg and within one month the tumor was no longer palpable, within two months the mammography confirmed the absence of tumor. In another case, the patient took 300 mg of CoQ10 for residual tumor (post non-radical surgery) and within 3 months there was non residual tumor tissue (Lockwood et al. 1994). This overt complete regression of breast tumors in the latter two cases coupled with further reports of disappearance of breast cancer metastases (liver and elsewhere) in several other case (Lockwood et al. 1995) demonstrates the potential of CoQ10 in the adjuvant therapy of breast cancer.

There are promising results for the use of CoQ10 in protecting against heart damage related to chemotherapy. Many chemotherapy drugs can cause damage to the heart (UTH 1998; ACS 2000; NCCAM 2002; Dog et al. 2001), and initial animal studies found that CoQ10 could reduce the adverse cardiac effects of these drugs (Combs et al. 1977; Choe et al. 1979; Lubawy et al. 1980; Usui et al. 1982; Shinozawa et al. 1993; Folkers 1996).

Caution: Some studies indicate that CoQ10 should not be taken at the same time as chemotherapy. If this were true, it would be disappointing, because CoQ10 is so effective in protecting against adriamycin-induced cardiomyopathy. Adriamycin is a chemotherapy drug sometimes used as part of a chemotherapy cocktail. Until more research is known, it is not possible to make a definitive recommendation concerning taking CoQ10 during chemotherapy. For more information please see the Cancer Chemotherapy protocol.

EPA and DHA

Dietary polyunsaturated fatty acids (PUFAs) of the omega-6 (n-6) class, found in corn oil and safflower oil, may be involved in the development of breast cancer, whereas long chain (LC) omega-3 (n-3) PUFAs, found in fish oil can inhibit breast cancer (Bagga et al. 2002).

A case control study examining levels of fatty acids in breast adipose tissue of breast cancer patients has shown that total omega-6 PUFAs may be contributing to the high risk of breast cancer in the United States and that omega-3 PUFAs, derived from fish oil, may have a protective effect (Bagga et al. 2002).

A higher omega-3:omega-6 ratio (n-3:n-6 ratio) may reduce the risk of breast cancer, especially in premenopausal women (Goodstine et al. 2003). In a prospective study of 35,298 Singapore Chinese women aged 45-74 years, it was determined that high levels of dietary omega-3 fatty acids from marine sources (fish/shellfish) were significantly associated with reduced risk of breast cancer. Furthermore, women who consumed low levels of marine omega-3 fatty acids had a statistically significant increased risk of breast cancer (Gago-Dominguez et al. 2003).

Omega-3 fatty acids, primarily eicosapentanoic acid (EPA) and docosahexaneoic acid (DHA) found naturally in oily fish and fish oil, have been consistently shown to retard the growth of breast cancer in vitro and in animal experiments, inhibit tumor development and metastasis. Fish oils have antiproliferative effects at high doses, which means they can inhibit tumor cell growth, through a free radical-mediated mechanism, while at more moderate doses omega-3 fatty acids inhibit Ras protein activity, angiogenesis, and inflammation. The production of pro-inflammatory cytokines can be modified by dietary omega-3 PUFAs (Mancuso et al. 1997).

High consumption of fatty fish is weakly associated with reduced breast cancer risk (Goodstine et al. 2003). Flaxseed, the richest source of alpha-linoleic acid inhibited the established growth and metastasis of human breast cancer implanted in mice. This effect was found to be due to its down-regulation of insulin-like growth factor I (IGF-1) and epidermal growth factor receptor (EGF-R) expression (Chen et al. 2002). The recommended dosage is to consume a fish-oil concentrate supplement that provides 3200 mg of EPA and 2400 mg of DHA a day taken in divided doses.

Vitamins A, D, and E

Vitamin A and vitamin D3 inhibit breast cancer cell division and can induce cancer cells to differentiate into mature, noncancerous cells. Vitamin D3 works synergistically with tamoxifen (and melatonin) to inhibit breast cancer cell proliferation. The vitamin D3 receptor as a target for breast cancer prevention was examined. Pre-clinical studies demonstrated that vitamin D compounds could reduce breast cancer development in animals. Furthermore, human studies indicate that both vitamin D status and genetic variations in the vitamin D3 receptor (VDR) may affect breast cancer risk. Findings from cellular, molecular and population studies suggest that the VDR is a nutritionally modulated growth-regulatory gene that may represent a molecular target for chemoprevention of breast cancer (Welsh et al. 2003).

Daily doses of vitamin A, 350,000 to 500,000 IU were given to 100 patients with metastatic breast carcinoma treated by chemotherapy. A significant increase in the complete response was observed; however, response rates, duration of response and projected survival were only significantly increased in postmenopausal women with breast cancer (Israel et al. 1985).

Breast cancer patients may take between 4000 to 6000 IU, of vitamin D3 every day. Water-soluble vitamin A can be taken in doses of 100,000-300,000 IU every day. Monthly blood tests are needed to make sure toxicity does not occur in response to these high daily doses of vitamin A and vitamin D3. After 4-6 months, the doses of vitamin D3 and vitamin A can be reduced.

Vitamin E is the term used to describe eight naturally occurring essential fat-soluble nutrients: alpha-, beta-, delta-, and gamma-tocopherols plus a class of compounds related to vitamin E called alpha-, beta-, delta-, and gamma-tocotrienols. Vitamin E from dietary sources may provide women with modest protection from breast cancer.

Vitamin E succinate, a derivative of fat-soluble vitamin E, has been shown to inhibit tumor cell growth in vitro and in vivo (Turley et al. 1997; Cameron et al. 2003). In estrogen receptor-negative human breast cancer cell lines vitamin E succinate inhibited growth and induced cell death. Since vitamin E is considered the main chain breaking lipophilic antioxidant in plasma and tissue, its role as a potential chemopreventative agent and its use in the adjuvant treatment of aggressive human breast cancers appears reasonable. Those with estrogen-receptor-negative breast cancers should consider taking 800-1200 IU of vitamin E succinate a day. Vitamin E supplementation, 800 IU daily for 4 weeks, was shown to significantly reduce hot flashes in breast cancer survivors (Barton et al. 1998).

Caution: Refer to the symptoms of vitamin A toxicity in Appendix A: Avoiding Vitamin A Toxicity. When taking doses of vitamin D3 in excess of 1400 IU a day, regular blood chemistry tests should be taken to monitor kidney function and serum calcium metabolism. Vitamin E has potential blood thinning properties, individuals taking anticoagulant drugs should inform their treating physician if supplementing with vitamin E and have their clotting factors monitored regularly.

Tocotrienols

When vitamin E was isolated from plant oils, the term tocopherols was used to name the initial four compounds that shared similar structures. Their structures have two primary parts--a complex ring and a phytyl (long-saturated) side chain--and have been designated as alpha, beta, delta, and gamma tocopherol. Tocopherols (vitamin E) are important lipid-soluble antioxidants that can protect the body against free radical damage.

However, there are four additional compounds related to tocopherols--called tocotrienols?that are less widely distributed in nature. The tocotrienol structure, three double bonds in an isoprenoid (unsaturated) side chain, differs from that of tocopherols. While tocopherols are found in corn, olive oil, and soybeans, tocotrienols are concentrated in palm, rice bran, and barley oils.

Tocotrienols elicit powerful anticancer properties, and studies have confirmed tocotrienol activity is much stronger than that of tocopherols (Schwenke et al. 2002).

Tocotrienols provide more efficient penetration into tissues such as the brain and liver. Because of the double bonds in the isoprenoid side chain, tocotrienols move freely and more efficiently within cell membranes than tocopherols, giving tocotrienols greater ability to counteract free radicals. This greater mobility also allows tocotrienols to recycle more quickly than alpha-tocopherol. Tocotrienols are better distributed in fatty cell membranes and demonstrate greater antioxidant and free-radical-scavenging effects than that of vitamin E (alpha-tocopherol) (Serbinova et al. 1991; Theriault et al. 1999).

Tocotrienol's antioxidant function is associated with lowering DNA damage, tumor formation, and of cell damage. Animals exposed to carcinogens that were fed corn oil- or soybean oil-based diets had significantly more tumors than those fed a tocotrienol-rich palm oil diet. Tocotrienol-rich palm oil did not promote chemically induced breast cancer (Sundram et al. 1989).

Tocotrienols possess the ability to stimulate the selective killing of cancer cells through programmed cell death (apoptosis) and to reduce cancer cell proliferation while leaving normal cells unaffected (Kline et al. 2001). Tocotrienols are thought to suppress cancer through the isoprenoid side chain.

Isoprenoids are plant compounds that have been shown to suppress the initiation, growth, and progression of many types of cancer in experimental studies (Block et al. 1992). They are common in fruits and vegetables, which may explain why diets rich in these foods have consistently been shown to reduce the incidence of cancer.

Isoprenoids induce cell death (apoptosis) and arrest cell growth in human breast adenocarcinoma cells (MCF-7) (Mo et al.1999). Isoprenoids may suppress the mevalonate pathway, through which mutated Ras proteins transform healthy cells into cancer cells. Mutated ras is the most common cellular defect found in human cancers. The mevalonate pathway escapes regulatory control in tumor tissue but remains highly sensitive to regulation by tocotrienols. Tocotrienols are at least five times more powerful than farnesol, the body's regulator of the mevalonate pathway. Interestingly, human breast cancer cells have been shown to respond very well to treatment with tocotrienols (Parker et al. 1993).

Tocotrienols cause growth inhibition of breast cancer cells in culture independent of estrogen sensitivity and have great potential in the prevention and treatment of breast cancer (Nesaretnam et al. 1998).

In vitro studies have demonstrated the effectiveness of tocotrienols as inhibitors of both estrogen-receptor-positive (estrogen-responsive) and estrogen-receptor-negative (nonestrogen-responsive) cell proliferation. The effect of palm tocotrienols on three human breast cancer cells lines, estrogen-responsive and estrogen-nonresponsive (MCF7, MDA-MB-231, and ZR-75-1), found that tocotrienols inhibited cell growth strongly in both the presence and absence of estradiol. The gamma- and delta-fractions of tocotrienols were most effective at inhibiting cell growth, while alpha-tocopherol was ineffective. Tocotrienols were found to enhance the effect of tamoxifen (Nesaretnam et al. 2000).

Delta-tocotrienol was shown to be the most potent inducer of apoptosis (programmed cell death) in both estrogen-responsive and estrogen-nonresponsive human breast cancer cells, followed by gamma- and alpha-tocotrienol (beta-tocotrienol was not tested). Interestingly, delta-tocotrienol is more plentiful in palm tocotrienols than in tocotrienols derived from rice. Of the natural tocopherols, only delta-tocopherol showed any apoptosis-inducing effect, although it was less than one tenth of the effect of palm and rice delta-tocotrienol (Yu et al. 1999).

Tocotrienols effectively arrested the cell cycle and triggered cell death of mammary cancer cells (from mice) whereas tocopherols (alpha, gamma, and delta) did not cause inhibition of tumor cell growth. Highly malignant cells were most sensitive to the antiproliferative effects of tocotrienols, whereas less aggressive precancerous cells were the least sensitive (McIntyre et al. 2000).

Tocotrienols were found to be far more effective than alpha-tocopherol in inhibiting breast cancer cell growth. Tocotrienols in combination with tamoxifen proved more effective than either compound alone in both estrogen-responsive and nonresponsive breast cancer cells. The synergism between tamoxifen and tocotrienols may reduce the risk of adverse side effect from tamoxifen (Guthrie et al. 1997).

Tocotrienols are considered important lipid-soluble antioxidants, with potent anticancer and anti-inflammatory activity. Therefore, a daily dose of 240 mg of tocotrienols should be considered as an adjuvant breast cancer therapy.

At www.lifeextension.com

chisandy

Tread carefully here, mysticalcity. Hate to disparage a fellow BCO-er by name, but the one you're quoting has a definite and sometimes vehement anti-conventional-medicine bias. (She was one of those whose political screeds got political discussion banned as a subject from nearly every BCO forum & thread). That article is full (excruciatingly, hyperextensively full) of pseudoscience. I dang near did a spit-take with my seltzer over its definition about tamoxifen's purpose and mechanism. It is prescribed to block tumor cells' estrogen receptors' access to estrogen, NOT to "reduce breast cancer metastases and improve survival!" Tamoxifen has nothing to do with metastases, and is NOT prescribed to treat them--that article is conflating that alleged purpose with that of aromatase inhibitors, which ARE given along with certain newer drugs known as CDK 4 & 6 inhibitors (Ibrance, Verzenio) once metastases are detected. There are also certain enzymes & antioxidant supplements touted in that article that are actually contraindicated in women being treated for ER+ breast cancer, and which can block the action of vital drugs used to treat it. (Of course, if you want to spurn actual medicine and roll the dice on alterna-nutrient therapy, I guess there are no drugs to inhibit. The odds on successfully going alterna-only are dismal).

LifeExtension.com is a quack site. Quackwatch.org (which has a breathtaking array of bull-pucky purveyors in all walks of healthcare) says so. It is a for-profit subscription magazine & website with pages and pages of supplement ads. The "Life Extension" principles have been slammed by ScienceBasedMedicine.org (and theskepticalcardiologist.com has an eviscerating article about it with the brilliantly funny subtitle "Would You Like Some Snake Oil With Your Redundancy?"). Wikipedia sets forth the founders Pearson & Shaw's discredited theories (and hucksterism), and quotes noted ACTUAL PHYSICIANS about how gerontology is a fertile breeding ground for peddlers of false hope.

Oh, and you might want to post a link rather than wasting time and space by making everyone scroll through a full-length rambling article. You're new here, so I suppose you didn't know the custom & etiquette here--so here goes: if you go to the top of your Reply box you will see a menu with font styles, spacing, margins, smileys, and a bunch of shortcut icon boxes. There's one for posting photos, one for videos, and one with a couple of little links in a chain. Click that one to post a link as part of your reply. It will direct you to paste the actual url into one box, and give the link a title in the other. Please, please use them from now on.

This is not the thread to tout alternative therapies--there's a whole separate forum topic for that (and I guess the member you quote is one of the most prominent poster there).

chisandy

Oh, and BTW: I have taken melatonin for years, still do (for natural sleep support). I adore coffee and all things caffeine. I used to take handfuls of those supplements (Vit. E, manganese quercetin, resveratrol, alpha-lipoic acid, vinpocetine, etc.) for supposed heart health and to treat a weird sensorineural hearing problem I developed after a cold. Even drank pomegranate juice and ate pomegranate seeds & blueberries. I still got breast cancer.

dogmomrunner

Geez what a long post. I’ve worked in research before and quite frankly you can make it say pretty much anything you want to. My husband and I have added some more natural remedies for my chemo SE but that does not mean the traditional medications and therapies are not used. And no way am Igiving up my coffee!

edj3

ChiSandy thanks for a reasoned response to that enormous wall of not scientific text.

It's so easy to grasp at "information" like that in hopes of making all this go away. Shoot, I *would* give up my coffee if that were the case! But it's a false hope. Yes, I can and do choose very carefully what I eat but I'm under no illusions that my cruciferous crunch salad is going to kill any stray cancer cells in my body.

I especially hate that this kind of "information" is something those who are running scared and feeling desperate will turn to and possibly reject the known medical interventions that will help them.

mysticalcity

Well I will definitely take the post down so no one reads more into it or is misled, but there are a lot of authenticated research studies about a number of natural remedies mentioned in the article that do help reduce estrogen levels--including many in the article like I3C, melatonin, vitamin D, curcumin etc. I was simply trying to point out if one makes the choice to stop AI treatment they could consider replacing that with potentially effective natural treatments. As my AI treatment commenced neoadjuvant I was able to measure my tumor response--I did do many of the things mentioned in the article along with my AI--I've spent thousands of hours researching clinical studies and implemented a natural regimen concomitant with my AI. My MO was shocked at my tumor reduction after 5 months on AI treatment--which she said "could well have been impacted by your other supplements". She said she's never seen such a great response.

salamandra

Hiya,

I'm in the boat of super struggling with tamoxifen (debilitating fatigue) and trying to figure out how hard to fight to stay on it. On the one hand, my oncotype puts me at a pretty low 10 year risk of distant recurrence, as my MO acknowledged (from 6% with tamoxifen to 9-12% without, her estimate). But the other thing that she pointed out, that I had been forgetting too and that I think sometimes gets lost:

The recurrence risk of ER+ cancer never goes away. Since I'm young (in breast cancer terms), she's thinking not only about the 10 year risk recurrence. I hope to have 40+ more years of my life. Metastasis in the next 10 years would suck for sure, but it would also suck in 15 years or 25 years or 35 years. Over the long term, it's possible that me finding a way to stay on tamoxifen for an extended time now could reap a much larger than 3-6% absolute benefit.

So... I'm on a one month holiday, per her recommendation. Then we will try ramping me back up slowly, and she is speaking with a psychiatric psych about med options for counteracting fatigue. We'll see.

Sigh.

chisandy

mysticalcity, just curious: why, with a 2cm stage IIA PR- tumor, do neoadjuvant treatment at all, and why AI rather than chemo or radiation? (And how was the node status--presumably the "A" in the stage--determined without biopsy)? Almost everywhere in the U.S. for non-metastatic breast cancer, hormonal therapy is post-operative. Did you get AI first in order to shrink the tumor below 1.5cm (the current upper limit for cryotherapy)? Cryo is not yet standard therapy for breast cancer: the theory of how it works (frozen cancer cells "burst" and release their contents throughout the body in order for the immune system to reject them and presumably "learn" to destroy cancers that may occur later) has not been proven in humans, only mice. The future-immune-system response is still a hypothesis. (Those "this is a cancer cell being destroyed by an immune cell" commercials may be striking--but are those red celll/blue cell graphics actual electron microscope photographs of human cancer & immune cells, or are they computer simulations)?

Initial ASCOG study response rate has been favorable, but still too recent to establish recurrence and mets stats. I certainly would not be comfortable with a procedure that releases cancer cells throughout the body and requires extreme faith in one's immune system to prevent those released cells from becoming metastatic. I might have rolled the dice had it been offered to me were I newly diagnosed now--but my tumor was 1.3cm, Stage IA, low-Oncotype and Luminal A-type: highly PR+ as well as ER+.

Are you by any chance being treated at one of the centers in the original 86-patient ASCOG study which closed after 3 years ("further evaluation is needed" was the conclusion) and never went on to a Phase 3 randomized trial for lack of funding; or at Margie Peterson or John Wayne by Dr. Holmes, who decided to pick up the ball and run a trial himself? His trial (FROST, funded by the device mfr.) is not randomized; it has 2 arms: >70 yrs. old, with cryo as the treatment endpoint; and 50-59, with radiation afterward. And the maximum tumor size at diagnosis (rather than time of cryo treatment) for both arms is 1.5 cm. It's not certain that a Luminal B tumor >2 cm at diagnosis would respond to cryo the same as one originally <1.5 cm de novo.

*A corollary caution would be the experience of the practice of "morcellating" fibroids (using a mechanical device to chop them up into tiny pieces that could be suctioned out) instead of removing & biopsying them; in many morcellated fibroids it turned out cancer cells in them were released and seeded elsewhere in the uterus--in many more locations than the original tumor. How come those women's immune systems were unable to "catch & kill" the cancer cells?

RobinLT

edj3, although the AIs weren’t the answer for me, I am pretty sure they are the way to go, if you can tolerate them. So I am not endorsing my decision for everyone. I am also very fortunate that my tumor was small and found early. If my cancer was larger and more aggressive, my decision to forgo the drugs would have been a scary one

RobinLT

movingsoccermom, You and I are examples of the many and varied ways that each of us experiences this journey. Another benefit of dropping the AIs is that I was then able to get off the antidepressant and sleeping aid. Feels great to simply feel like myself again. Glad you are doing well too

RobinLT

PontiacPeggy, I think the cognitive problems, for me, were due to the loss of estrogen. So... the drug itself is safe, but the resulting loss of estrogen can be trouble for some of us. There is a family history of dementia, but not cancer. So... maybe I am predisposed to head down that super slippery slope.

RobinLT

ChiSandy, You look fabulous, your own self! And you are right. I lucked out in the cancer wheel of fortune. I say I had cancer (lower case cancer) and so many had Cancer, capital C and bold. I shared the waiting room for radiation with women who humbled me. And without exception, they were all strong and positive and brave. I felt honored to share their company.

These days, I feel great, fully mentally present, energy and sass is back. I am chubbier, but I don’t sweat the scales much anymore. I am too lucky to complain. Thanks again for your support.

benji69

ChiSandy you always have good information. I watch for your posts.