Iodine, thyroid, and breast cancer??
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Good reminder anom about the detox symptoms. I got a nasty headache the first day I took 1000 mg of vitamin C. I often have cloudy urine, and that is also a sign of bromide detoxing. As we increase our levels of iodine, we will displace the other halides that have set up camp (bromine, chlorine, flouride, perchlorate). Drink plenty of water and keep things moving along the instestinal tract.
I think an iodine pamphlet is a great idea. I just finished Brownstein's book on iodine and I was so disappointed that there was no explanation as to why the USDA deems iodine to be toxic starting at 1100 mcg. It's clearly bogus information and in all the learning I've done regarding iodine for over a year now, I've never seen one mention of a reason or a source of where this ridiculous information came from.
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Hi Carol,
I just joined this site yesterday and am reading to catch up!!! I saw your Feb. post about what iodine you are taking and about poss. getting off synthroid. I vowed when my mom died from colon cancer in 2002 that I would not be on any prescription drugs b4 75 however in 2005 they diagnosed an enlarged thyroid and i had one lobe removed to make sure it was not cancer. It was not but now I have bc as of dec. 08 and am seeing the overwhelming connection. I did not want to stay on synthroid and hoped one lobe would take over. when i asked my endocrin. how could one lobe take over if i never give it a chance. She said, "don't complain i have patients on tons of meds. and you are only on one!!!" Duh!! I want to be so healthy i am on none. I am supposed to start Tamoxifen and do not want to. I am researching iodine and DIM. How are why will you get off the synthroid?
Danette
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Hi,
I finished Radiation in February of this year, and at the end of March I had a swollen neck..I thought it was lymph nodes, but now I have a hypothyroidism. I think the radiation caused it. I am on synthroid now and feel much better and my neck isn't swollen.
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Oh my, no calcium!!!! What about us osteopina girls???? These supplements are getting quite confusing.
Patty
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Anom! that is so funny about the cholesterol!! I didn't want to be tagged as a conspiracy theorist, but I have always felt that when high cholesterol came into the spotlight it was when all of the ads for the statins were on TV blah blah blah, it just seems too convenient! but that is a whole other story!
So, my muti vitamin has 45mg of B1 and 40mg of B2 and 50mg of low-flush fast release Niacin then the Metanx has 2.8mg Folic Acid 25mg of B6 and 2mg of B12, I am just trying to figure out where the ATP would come in, I don't want to OD LOL!! Althea, thanks for the info awesome! I do have Dr. Strands' book, love it! I take CoQ10 also, along with tumeric, DIM, D3. I now rattle when I walk! Actually my husband saw my pile 'o' supplements the other morning as I got them out to take, his face was a picture!! He was a little concerned that I take so many, I told him its my medicine!
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Amon, you seem to be the iodine expert here...which is appreciated for those who have so many questions regarding the thyroid and iodine. My iodine blood test was normal. The autoimmune test was slightly elevated. I am not sure how all this plays into hypothyroidism and the breast cancer connection. My naturalpathic doctor is doubling my iodine intake. I am also taking 60m of Armour. Do you have knowledge on how the autoimmune disorder affects the iodine level in the body?
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Lorainne, Stop going to that board!!!! You need serenity, not freak outs!!! Just say NO!!! LOL.
My cholesterol overall was 210 and I eat nothing to cause this and walk or eliptical 20 miles a week! GP was not concerned. Said the Good cholesterol was really high, and the bad was not that high, so I am taking no meds for this. Just FYI!
Anom, thank you for that pointer to Dr. F statements on what happens to the TSH, T3 and T4 when starting iodine. I have been crashing too much, so something has changed. My GP is allowing me to move from synthroid to dessecrated thyroid, so I am going to try that. But I am going to read Dr. F's whole article there that you pointed me to.
Thank you!!
Barry, I was going to take Nature-Throid vs. Armor as on another site (StopTheThyroidMadness.com) there were reports about a recent reformulation of Armor and it not working for some people. Did you experience that? Also, did you ever experience any availability issues with Armor? They were talking about that too...
Spring.
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Thanks Spring!
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Hey girls, I have been so busy, just trying to catch up here. It sometimes makes me mad when I come here and learn so much from you all that we do not have doctors to tell us this stuff! But at least none of us has to worry about co pays here! LOL So keep the free advice coming!
Althea-I too love Dr. Strand's philosophy. He is one of the first doctors I read, and it made so much sense to me. He gave me a lot of confidence in listening to my inner voice struggling with decisions. I like how he talked about how the problem with most studies is that they will isolate one element, Vit. C for example, and do a trial, but not take into account that there is more than one factor in any result. It is like putting the finger in the dike. Just because you plug up one hole, it does not mean you can ignore the others. I thought his supplement guidelands were great, and I follow them pretty closely. And I agree with anom about the cholesterol. I have read several books that seem to dismiss the theory that cholesterol count is a big deal. The whole thing was another ploy by the drug companies to sell all those statins. They needed a test to validate them. Homosystine levels are much more relevant and those are the tests that should be run, which few doctors do. But there is no drug for homosystine. Basically, diet and exercise can lower this.
My own cholesterol actually got higher after I changed my diet. Like you Spring it is around 200 and I have really good H levels. So I am not even worried about it. I just keep taking that omega 3.
Back to the iodine. When I went through some detox headaches, as Anom said, I did the salt loading and they went away. All I did was swallow about a teaspoon of sea salt and then chase it with a lot of water. It worked! I went a way for a the last couple of days and I forgot my "meds" and my head was throbbing! Do you think I am "Hooked" and I was having a junkie reaction???
Fairy -My compounding pharm has his own BHRT formula. It is a balance of estrogen and progesterone. I bought some, but have not tried it yet. He really believes that it is essential for bc survivors and he uses recommendations from Dr. Lee so I feel I can trust his formula. I just have not taken the plunge yet. How are you doing on yours?
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Vivre, posted on the other thread re: progesterone! My naturopath gave me Metanx for my slightly elevated homosystine level, its prescription B's and Folic Acid, she will retest next month. Did your compounding pharm make the cream just for you, based on your particular levels, or is it his standard formula that he feels is the right combo? I am off to continue packing, we are moving, I am excited, but HATE packing aaaaahhhh!!!! I will check in later! hugs!
L
ox
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L-It is a standard compounded formula. I think the theory is the proportions are the same, but you use more or less, depending on how you feel, and then how your follow up tests look.
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Barry,
The so-called auto-immune seems stuff seems to be a non-issue.
Are you on Stephanie's Yahoo Iodine Group? They'll tell you the same thing. They give iodine to people with auto-immune Hashi's or Graves. Your doc is doing everything right. You are so lucky!
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anom- what did you mean when you said the so-call auto-immune??? Is it all hype? The auto-immune scares me. I am imaging my immune system attacking my thyroid. My doc is giving me another pill that is supposed to decrease the affects of the auto-immune disease.
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Barry,
You need to go to the Yahoo Iodine Group:
This is a description:
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As of 2009, The Iodine Group has almost 3000 members interested in understanding how to use iodine for the health of the body. The members include medical practitioners, researchers, people with various health challenges, and people interested in improving total body health.
Most members are from the US, but there are also members from many other countries.
The Iodine Group has hundreds of links to a wide range of references. For example, there are links on various sources of iodine (e.g., seaweed, dairy, salt, Lugol's, Iodoral, Iosol, Cayce formulas, etc.), cautions when supplementing with iodine, other nutrients that are especially important when supplementing (e.g., selenium, magnesium, iron, Vitamins C and A), and general clinical guidelines.
The Iodine Group has an active and supportive email community with an extensive email archive. It is a great place to post your own personal questions about how to use iodine and to share your personal experiences.
If you are interested in learning more about iodine, please join us:
http://health.groups.yahoo.com/group/iodine/
---------------------------------------------------------------------------------------------Dr. Brownstein treats Hashi's autoimmune with iodine and an amino acid whose name I can't remember. That's probably what your doc is giving you.--
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Fairy writes:
So, my multi vitamin has 45mg of B1 and 40mg of B2 and 50mg of low-flush fast release Niacin then the Metanx has 2.8mg Folic Acid 25mg of B6 and 2mg of B12, I am just trying to figure out where the ATP would come in, I don't want to OD LOL!!
The ATP CoFactors have 500 mg of a special no flush niacin (B3). So your multi doesn't have nearly enough. ATP has 100 Mg of B2. I don't think you can overdose. The ATP is just boosting your multi in the right places to maximize your iodine absorption. You pee away what you can't use.
Also, beauty mavens, B1 is the lip vitamin. Honest.
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Thanks Anom! So just to confirm, I could do both the multi, the Metanx and the ATP CoFactors along with the iodine? What do you mean by lip vitamin? 0
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I am showing my ATP cofactor bottle with
- B-2 Riboflavin 100mg
- B-3 Niacin as inositol hex...) 500mg.
There is no B1. I think B1 is Thiamin? Yes: http://en.wikipedia.org/wiki/Thiamine
Spring.0 -
Spring is right. I mistyped or my brain misfired. The AC is out. I just edited my previous post.
Then I typed this and it didn't send. I should quit while I'm behind!
Fairy, that doesn't sound like many vitamins at all. I take extra magnesium, chromium and 4,000 units D3. And fish oil. Did I mention Livon C?
If you can see thru your supplement bottles to your kitchen counter you're not taking too many supplements.
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Fairy,
B1 is a vitamin used to keep your lips from peeling or looking old. Honest.
You probably don't need it. Wrinkly lips run in my family. An alt med told me to take extra B1 years ago along with other Bs when he saw my lips were peeling.
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I was just reading in some Thyriod book about B1 as well. So I ordered some. !!! I can't stop!!!! ahhhck!
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I am currently investigating my own thyroid function and am really enjoying this link - thank you all for the wisdom! I already know that I have a multinodular goitre and hypothyroidism might account for my low energy levels over the past 10 years or so. I am gearing up for Iodoral but am looking for anything else I can do to help myself. Since moving to the US from London, I was caught unawares by the fact that fluoride has been added to all the drinking water in the US. I had been carefully removing chlorine, bacteria, parasites and heavy metals but totally ignoring THE FLUORIDE. Since diagnosis I have been drinking RO water as fluoride has an undesirable effect on the thyroid. That affects our thyroids, our pets, birds and wildlife. Are you guys drinking the water straight?
Here is a link you guys might find interesting: www.fluoridealert.org/health/thyroid/
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Wooly,
Thanks for the link. The reason fluoride suppresses the thyroid is because it suppresses iodine uptake to the thyroid. I only drink bottled water here in the US.
Fluoride also competes for iodine receptors in the breast and if you're iodine deficient the fluoride will win.
You mean the UK doesn't f'luoridate the water? Lucky you. You need to bring your UK water with you!
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being from England myself, I think there are a LOT of things we don't do over there, that they do here, makes you wonder.........
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Thanks for the link wooly. I feel very lucky that I get my water from my own well. I have a very good whole house softener that takes out the heavy minerals and then I have a triple osmosis system for drinking and cooking. My tea is very clear! I wonder how it is in France. I have a French student with me now, who is very beautiful but she has those white marks on her teeth which indicate early exposure to too much flouride. She is very self conscience of it. I wonder if she can get rid of it?
I am happy to report that I have been really sleeping great. I think the iodine has really kicked in. I stopped taking melatonin. Anon, have you heard about melatonin having any effect on eyesight? I have been trying to find some info after hearing that from a friend, but have not been able to find a thing. My eyes have really gotten worse over the past year. I wonder if the BHRT will help with that? I am still on the fence because I do not have any hot flashes and am sleeping pretty well-still waiting for your report Fairy. LOL My compounding pham insists that it is so protective, but I want to add one thing at a time then do tests so I can see what effect it has. I am going to wait to see if my numbers have changed with the myomine and see how the iodine results look.
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Wooly, please be careful with R/O water. Because it pulls out all of the (mostly alkaline) minerals in water, it often has a very low pH. Low pH = low oxygen intake, which creates a whole other set of problems.
I started drinking bottled water recently, after quizzing the water bottling company's engineering department about how they process water, what the pH was, what types of bottles they use, etc. Our tap water's pH was too low, and R/O filters are too expensive, so I was kind of out of options.
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vivre - I just read that curcumin is good for eyesight. It also good for us bc girls. I also read that women on hrt for more than 3 yrs have a greater chance of recurrence of bc. I was on hrt for 11 years!!!
Curcumin was highly recommended for us hrt girls. I guess it will always be something to worry about.Patty
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Reposting in reply to Vivre asking if her friend who is starting chemo could enroll in the proposed trial in which one group would get chemo and the other group would get chemo and iodine.
Vivre,
I'm told the iodine + chemo clinical trial is on hold (get this!!!) because the FDA objected the iodine might be toxic to the thyroid.
The FDA is okay with giving both groups chemotherapy and they think the iodine might be toxic to one group? Are you kidding me?????
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Patty writes: I also read that women on hrt for more than 3 yrs have a greater chance of recurrence of bc.
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Patty, where did you read that? That is the exact opposite of the truth. Women who have been on HRT have a much better survival because the hormones "differentiate the cells". These results have been dupicated in several studies. Note in the article below: 100% of the HRT takers were still alive after ten years. Only 90% of the non takers were alive.
Improved breast cancer survival among hormone
replacement therapy users is durable after 5 years of
additional follow-up
Dara Christante, M.D., SuEllen Pommier, Ph.D., Jennifer Garreau, M.D.,
Patrick Muller, B.S., Brett LaFleur, B.S., Rodney Pommier, M.D.- American Journal of Surgery, Oct 2008We previously reported that breast cancer patients who used hormone replacement therapy (HRT) had significantly lower stage tumors and higher survival than never-users. We present an update with longer follow-up, HRT use data, and in vitro research.MethodsOur database of 292 postmenopausal breast cancer patients was updated to include HRT type, duration, and disease status. In vitro effects of estrogen (E) and/or medroxyprogesterone (MPA) on breast cancer cell growth were measured.ResultsTumor prognostic factors were better and survival rates higher for both E and combination HRT users of any duration. Use greater than 10 years correlated with node-negative disease, mammographically detected tumors, and 100% survival. E supported minimal proliferation; MPA induced cell death; E+MPA results were similar to E alone.ConclusionsHRT users, regardless of type or duration of HRT use, continued to have higher survival rates. In vitro results supported the clinical finding that outcomes for users of E and E+MPA were similar.We previously reported that breast cancers in hormone replacement therapy (HRT) users were smaller, lower grade, more often node-negative, lower stage, and had significantly higher survival rates compared to those in never-users.1 Recent events have raised concerns about the impact of HRT on breast cancer. Particular concern has been raised about the use of combinations of estrogen (E) and medroxyprogesterone acetate (MPA). Results from the Women's Health Initiative (WHI) trial indicated that breast cancers were more advanced among users of E and MPA (combination HRT) than among patients receiving placebo.2 This would be expected to result in lower survival rates among users of combination HRT. Concerns also exist about duration of HRT use and breast cancer.3, 4Due to these concerns, we investigated if the higher survival rate we reported was durable after an additional 5 years of follow-up. We also investigated whether duration or type of HRT are associated with differences in tumor characteristics or survival rates. We have supplemented our clinical investigation with in vitro studies in which estrogen receptor (ER)-positive and -negative breast cancer cell lines were treated with various concentrations of E, MPA, or combinations of E and MPA to determine their impacts on cellular proliferation.MethodsOur database of 292 postmenopausal women diagnosed with breast cancer at Oregon Health & Science University between March 1994 and January 2002 from our previous publication1 was updated by review of medical records. New data included the current disease status of each patient as well as the type and duration of HRT used. HRT was categorized as E alone, progestin alone, E and progestin combination, or other HRT. If E and progestin were ever taken by a patient, either serially or concomitantly, it was considered combination HRT. Approval for this retrospective review was obtained from the institutional review board.Disease-specific survival curves were constructed using the Kaplan-Meier method5 and statistical significance between survival distributions was determined by log-rank analysis. Significance of differences between groups of patients was determined by chi-square analysis, Student t test, analysis of variance (ANOVA), Mann-Whitney U test, or Kruskal-Wallis H test. Correlations between duration of HRT use and tumor size, number of positive lymph nodes, and stage were determined using Pearson or Spearman coefficients of correlation. The independent effects of prognostic factors and HRT use on survival was determined by Cox regression analysis.For all laboratory experiments, 3 cell lines, T-47D, HCC1954, and HCC1937, were obtained from the ATCC (American Type Culture Collection, Manassas, VA) and maintained according to ATCC protocol. T-47D cells are ER-positive, progesterone receptor (PR)-positive; HCC1954 and HCC1937 cells are ER-negative, PR-negative; both are androgen receptor (AR)-positive.6 Cell lines with these receptor profiles were selected for study because our group of HRT users with a higher survival rate was comprised of a mixture of patients with ER-positive and ER-negative tumors. Cells were plated onto 96-well plates with 104 cells per well, grown in hormone-depleted media for 3 days, and then treated with 17-β-estradiol (E) and medroxyprogesterone-17-acetate (MPA) (Sigma-Aldrich, St Louis, MO).The dose-dependent effects of MPA were initially tested by treating ER-positive (T-47D) and ER-negative (HCC1937) breast cancer cells with a range of MPA (.01, .1, 1, 10, 100, and 250 nmol/L). In all subsequent experiments, T-47D and HCC1954 cells were treated with E alone at concentrations of 1 and 10 nmol/L or MPA alone at concentrations of 1, 10, 100, and 250 nmol/L. Cells were also treated with 1 or 10 nmol/L E in combination with 1, 10, 100, or 250 nmol/L MPA. For all experiments, cells grown in hormone-depleted media served as an untreated control. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and expressed as the relative percent change between treated and untreated cultures.7 All experiments were performed in triplicate wells and repeated a minimum of 3 times. Statistical significance of differences in proliferation of cell cultures was determined by ANOVA and independent t tests.ResultsOf the 292 patients, 144 reported HRT use at the time of diagnosis or anytime in the past. Seventy-three patients (51%) used E alone, 54 (38%) used combination HRT, 3 (2%) used progestins alone, and 14 (9%) used another type HRT (Table 1). There were no significant differences in the types of HRT used between patients with ductal carcinoma in situ (DCIS) or invasive cancer. There were no significant differences in the incidence of ER-positive or PR-positive tumors between HRT users and never-users. Data on HER2 status was not available for many patients whose diagnosis preceded the advent of traztuzumab therapy.Table 1.Comparison of prognostic factors and survival rates between never-users and HRT users by HRT type and duration[editors note: see full text article for omitted charts]Among patients with invasive cancers, mean tumor size, nodal status, ER and PR status, the presence of distant metastases, stage, and the method of detection did not vary significantly by types of HRT. Tumors of patients using either E alone or combination HRT were smaller than those of never-users (P = .022 and .003, respectively). There were significantly more T1 (≤2.0 cm) tumors among patients using E (P = .036) and combination HRT (P = .001) compared with never-users. Negative lymph nodes were significantly more common in users of E (P = .045) and combination HRT (P = .023) than in never-users. The mean number of positive lymph nodes was also significantly lower in users of E (P = .03) and combination HRT (P = .02) compared with never-users.There were no significant differences in the distribution of stage based on type of HRT use. Compared to never-users, users of E or combination HRT had significantly more cancers lower than stage II (P = .01 for both). The incidence of distant metastases did not differ between never-users and HRT users, whether compared collectively or by type of HRT.Data were available on the duration of HRT use for 133 of 144 users (92%) and the median duration was 7 years. Forty-seven patients (33%) used HRT for less than 5 years, 36 patients (25%) used HRT from 5 to 10 years, and 50 patients (35%) used HRT for more than 10 years. DCIS was evenly distributed between groups of HRT duration. Tumor size, number of positive lymph nodes, and stage did not increase with increasing durations of HRT use, regardless of type. Lymph node status was more often negative in patients with greater than 10 years of HRT use compared to never-users (P = .023). E and combination HRT users were more often diagnosed by mammography than palpation compared to never-users (P = .036 and .01, respectively). Patients with any type of HRT use for more than 10 years were also significantly more likely to have their tumors detected by mammography than by palpation compared to never-users (P = .01).After an additional 5-years of follow-up, the disease-specific 5-year survival rate of HRT users was 92% compared with 84% for never-users (Figure 1, P = .02). No patient with a diagnosis of DCIS had died of breast cancer. Among patients with invasive cancers, the 5-year survival rate of HRT users was 91% compared with 83% for never-users (P = .04). There were no significant differences in survival between patients grouped by HRT type. The 5-year survival rates for users of E and combination HRT were 89% and 95%, respectively. The difference in survival rates between combination HRT users and never-users was statistically significant (P = .04), but the difference in survival rates between users of E and never-users was not significant. Survival curves by type of HRT are shown in Figure 2 and compared with the curve for never-users.Figure 1. Survival curves for breast cancer patients who were HRT users (circles) compared with never-users (vertical dashes). The difference in survival was statistically significant (P = .02).Figure 2. Survival curves for HRT users of E (circles) and combination therapy (triangles) compared with never-users (vertical dashes). The difference in survival between patients who used combination therapy and never-users was statistically significant (P = .04).Survival curves of patients grouped by durations of HRT use of <5, 5-10, and >10 years are compared to the survival curve of never-users in Figure 3. Patients with more than 10 years of use had a 100% survival rate compared to 84% among never-users (P = .01).Figure 3. Survival curves for breast cancer patients based on duration of HRT use. Patients with varying durations of use <5 years (circles), 5-10 years (triangles), or >10 years (boxes) are compared to never-users (vertical dashes). The difference between patients with >10 years use and never-users was statistically significant (P = .01).Among patients with tumors detected by palpation, there was no significant difference in 5-year survival rates between never-users and any group of HRT users (Table 1). Among patients with invasive tumors detected by mammography, the 5-year survival rate for HRT users was 100% compared with 90% for never-users. (Figure 4, P = .03). To estimate the magnitude of difference in survival that could possibly be attributed to differences in adjuvant therapies between these 2 groups, data for each never-user with a mammographically detected tumor were entered into Adjuvant! Online, standard version 8.0.8 The maximum potential benefit of adjuvant therapies was recorded for each patient. The calculated median and mean decreases in survival had maximum adjuvant therapies been completely withheld from all never-users with mammographically detected tumors were 3.0% and 5.6%, respectively, at 10 years.Figure 4. Survival curves for patients with breast cancers detected by mammography comparing HRT users (circles) to never-users (vertical dashes). The difference in survival between HRT users and never-users was statistically significant (P = .02).Cox regression analysis was performed using variables of tumor size, tumor stage, nodal status, stage, mode of detection, receptor status, and HRT use. The only variable that was a significant independent predictor of survival was stage.In vitro responses to treatment with E and MPAExposure of the T-47D cells to 1 nmol/L E demonstrated 23% and 25% proliferation on days 5 and 8, respectively, compared to untreated cells. Treatment with 10 nmol/L E was inhibitory; cell growth decreased by 5% and 15% by days 5 and 8, respectively. MPA treatment alone did not have a proliferative effect at any concentration. Treatment with MPA and 1 nmol/L E resulted in 15% and 36% growth on days 5 and 8, respectively, which was not statistically different from the proliferation observed with 1 nmol/L E alone (P = .13 and .43, respectively). Treatment with MPA plus 10 nmol/L E resulted in significant cell death by day 8, an effect that increased with higher concentrations of MPA. Growth inhibition reached 50% and 42% by day 8 at concentrations of 100 nmol/L and 250 nmol/L MPA, respectively.In HCC1954 cells, in contrast to what was observed in T-47D cells, exposure to both concentrations of E was cytotoxic. However, similar to what was observed with T-47D cells, MPA treatment alone did not induce proliferation at any concentration. When cells were treated with E and MPA in combination, some variation in response was observed. The addition of MPA, at all concentrations, blunted the cytotoxic effect observed with 1 nmol/L E treatment alone but did not induce significant proliferation. Treatment with MPA and 10 nmol/L E did not significantly alter the cytotoxicity observed with 10 nmol/L E alone. The mean responses of both T-47D and HCC1954 cells to the various hormonal treatments are summarized in Figure 5. There were no significant differences between the results seen with E alone or E+MPA.Figure 5. Mean percentage change in proliferation of HCC1954 (black) and T-47D (gray) cells compared to untreated cells after 8 days of treatment with 17-β-estradiol (E), or medroxyprogesterone-17-acetate (MPA), or E+MPA. *Statistically significant changes compared to the untreated group. Differences between cells treated with E alone and E+MPA were not statistically significant.Dose-dependent cell death was observed in the ER-negative and ER-positive cell lines with increasing concentrations of MPA. By day 8, the percentages of cell death were -48%, -57%, -69%, -70%, and -73% for ER-negative cell line and -9%, -17%, -23%, -18%, and -16% for ER-positive cell lines at MPA concentrations of .01, .1, 1, 10, and 100 nmol/L, respectively.CommentsAfter an additional 5 years of follow-up, the survival rates for HRT users were still significantly higher than for never-users. Shuetz et al. also recently reported significantly higher 5-year survival rates of 93% for HRT users compared to 82% for non-users. The 5-year survival rates for the 2 groups reported in that study were remarkably similar to the rates reported in this study. In their study of 1,072 women, Shuetz et al also found a decreased incidence of metastatic disease among HRT users compared to non-users. The presence of distant metastases did not differ between HRT users and never-users or among users of different types of HRT in this study, but there were relatively few stage IV patients in the database.In this study, the higher survival rate was observed chiefly among patients with mammographically detected invasive tumors whose survival rate was still 100%, as it was in our previous report. In contrast, the 5-year survival rate for never-users with mammographically detected invasive tumors was significantly lower at 90%. Additional follow-up has not shown a change from our previous report in which there was no significant difference in survival rates based on HRT use among patients with invasive tumors detected by palpation.Given that the higher survival rate was found among mammographically detected tumors and that the frequency of screening mammography between HRT users and never-users was equal,1 the difference in survival is unlikely to be due to better screening of HRT patients. It is also unlikely that the higher survival rate is due to differences in adjuvant therapies. The calculated median and mean decreases in survival had maximum adjuvant therapies been completely withheld from all never-users with mammographically detected tumors were 3.0% and 5.6%, respectively, at 10 years. The observed difference in survival rates for mammographically detected tumors in our series was 10% and it occurred at less than 4 years. Thus, the difference in survival is greater in magnitude and occurs sooner than would be expected from differences in administration of adjuvant therapies.Tumor size,10 nodal status,10 and stage11 are strong independent predictors of breast cancer survival in large databases. In our series, HRT users had smaller tumors, more node-negative tumors, and lower stage disease than never-users. Regression analysis revealed that only stage was an independent predictor of survival in our database. This indicates that the higher survival rate of HRT users is chiefly attributable to lower stage disease resulting from combinations of small tumors and node-negative tumors.Several investigators have reported tumor size to be significantly smaller among HRT users12, 13, 14, 15, 16 but did not differentiate by HRT type. Others have reported lower incidences of positive nodes among HRT users.13, 15, 16 It is the report by Chlebowski et al2 from the WHI trial that has been in contradiction to most published observational studies. They reported more advanced tumors among users of combination HRT compared to women taking placebo (patients in the placebo group were not required to be never-users). Combination HRT users had a mean tumor size of 1.7 cm and a 26% incidence of positive nodes of compared with a mean tumors size of 1.5 cm and a 16% incidence of positive nodes in the placebo group. Although the 2-mm difference in mean tumor sizes was statistically significant, it may be of little clinical significance because both would correspond to T1c tumors.11 The statement that tumors are more advanced in combination HRT users is therefore derived primarily from the 10% higher incidence of positive nodes. There is a strong relationship between mean tumor size and the incidence of positive nodes, so this large shift in the incidence of positive nodes with only a 2-mm difference in tumor size is difficult to explain. The interpretation of the data has been that the placebo group is normal and, by comparing the combination HRT group to them, we must conclude that HRT made the tumors more advanced for their size than they otherwise would have been. This conclusion appears strengthened by the fact that it is derived from the only randomized prospective data available.The validity of this conclusion can be tested against other databases. Based on data from 257,888 breast cancer patients in the Surveillance Epidemiology and End Results (SEER) database, the correlation between mean primary tumor size and the percentage of patients with positive lymph nodes has been accurately described by the equation: percentage of patients with positive lymph nodes = 65.6107594/1+8.336998433e-0.1005638804(tumor size in mm).10 If one enters the mean tumor size of 17 mm for the combination HRT group into this equation, then the expected incidence of positive lymph nodes is 26%, which is precisely what was observed. This would indicate that the tumors in the combination HRT group were not more advanced for their size than other breast cancers. In contrast, if one enters the mean tumor size of 15 mm for the placebo group into the equation, then the expected incidence of positive lymph nodes is 23%. This does not agree with the observed rate of 16%. The data point for the placebo group falls well below the curve described by the equation. It is not plausible that placebo made tumors less aggressive than expected, so this indicates that the placebo group may not have been a typical sample of breast cancer patients. In light of the SEER equation, an alternative explanation of the WHI data is that the combination HRT group had typical breast cancers and the placebo group, for some reason, had an unusually low incidence of positive nodes. This had the effect of making the combination HRT group look worse than it actually was. The observed incidences of positive nodes for our patient groups were in close agreement with the predictions of the SEER equation, indicating that we had typical samples of breast cancer patients in our series.Data on the impact of the duration of use of HRT on breast cancer prognostic factors and survival are limited, but no differences have been reported.16 In our study, duration of use did not worsen any prognostic factor regardless of whether patients were considered together or grouped by type of HRT used. When patients were arranged in groups by durations of use, those with greater than 10 years of use were significantly more likely to have negative nodes and to have tumors that were detected by mammography.Although there were no statistically significant differences in survival rates among HRT users based on the type of HRT used, patients who used combination HRT had significantly higher survival rates than never-users. Users of E HRT also had higher survival rates than never-users, but the difference did not achieve statistical significance.Tissue culture results showed that 1 nmol/L E alone resulted in significant proliferation of ER-positive cells. In contrast, 10 nmol/L E alone consistently resulted in significant decreased proliferation of ER-positive cells. We have previously reported that concentrations between 1 nmol/L and 10 nmol/L support proliferation of ER-positive cell lines. Interestingly, in cultured breast cancer cells that have acquired anti-estrogen and aromatase inhibitor resistance, unexpected cytotoxicity has been observed in cells with normally proliferative concentrations of E, which may explain the observed results.17, 18 As expected, significant proliferation of ER-negative cells was not induced by treatment with E alone.No concentration of MPA induced a proliferative effect in any of the cell lines. When cells were treated with combinations of MPA and E, the net effects were no different than when they were treated with E alone. For example, when ER-positive cells demonstrated proliferation with 1 nmol/L E, the addition of MPA did not alter this proliferative effect. Similarly, when E treatment induced growth inhibition in either ER-positive or ER-negative cells, the addition of MPA did not alter this effect to the point where significant cellular proliferation was observed. If E induced growth inhibition in either ER-positive or ER-negative cells, the addition of MPA never resulted in significant stimulation of proliferation. Our data indicate that observed net effects on growth were driven by the concentration of E used and not by MPA. Maximum serum concentrations of MPA in patients are dose-dependent and range from 1.2 pg/mL to 4.8 pg/mL (.003-.01 nmol/L).19 In this study, the concentrations of MPA used for in vitro testing were within and above the range measured in patients.A limitation to these experiments is that the only effect of hormonal treatment that was measured was cellular proliferation. The effects of hormones on numerous other prognostic factors such as cellular differentiation, potential to metastasize to lymph nodes or distant organs, and interactions between tumor cells and supporting tissues were not tested in this in vitro model. The impact of hormones on these other factors was derived from the clinical outcomes measured in the study. Even the finding that E can support proliferation of ER-positive cells must be viewed in the context of an in vitro model. In this environment, cells are viable for only a short period of time when grown under minimal conditions that are supplemented with E only. Extending proliferation for longer periods requires the addition of growth factors and multiple other hormones to support the growth of breast cancer cells over time. However, the results of our in vitro studies support our clinical findings that the addition of MPA to E does not produce outcomes significantly different than those observed with E alone.In this study, we found that the higher survival rates of breast cancer patients who used HRT were durable after an additional 5 years of follow-up. Higher survival rates of HRT patients were found chiefly among patients with mammographically detected tumors. Both E and combination HRT use were associated with smaller tumors, a lower incidence of positive lymph nodes, and lower stages of breast cancer. Greater than 10 years of HRT use was also associated with more mammographically detected tumors and a 100% survival rate. Users of combination HRT did not have more advanced tumors than users of E alone or never-users. These clinical findings are supported by in vitro experiments in which the addition of MPA to E did not alter the effects observed with E alone.
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WOW, thanks anomdenet. That sure makes me feel better. Of course I don't remember where I read that considering it was yesterday or the day before!! My memory is terrible. I guess I should get some progesterone cream!!!! Heck, after reading that information, I should just go back on hrt,lol.
Patty
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Anom, thanks for the great summary. Is there a link I can use? I am saving them.
Sometimes our threads seem to go around in circles here and I can't remember what was where. LOL Someone mentioned about using club soda? I use mineral water, not club soda. Are you saying they are the same thing? They taste very different.
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