The Women's Health Initiative study suggested that taking estrogen modestly increases the risk of breast cancer in post-menopausal women. But estrogen is a double-edged sword. High doses actually shrink breast cancer! Learn more from my CTV.ca/health blog, originally posted in 2009.

​Treating advanced breast cancer: The estrogen paradox
by Dr. Lorne Brandes  August 24, 2009 

Is anything in science and medicine ever completely new? Occasionally, perhaps, but usually not. As a biblical sage once observed (Ecclesiastes 1:9-14): “What has been will be again, what has been done will be done again; there is nothing new under the sun.”
So, when a new study, showing that estrogen treatment can shrink advanced breast cancer, appeared in this week’s edition of the Journal of the American Medical Association (JAMA), the words of the sage immediately came to mind.
To put the study’s findings into context, we must first review the causal relationship between estrogen and breast cancer.
Large, widely-reported studies have shown that taking estrogen as part of hormone replacement therapy (HRT) significantly increases breast cancer risk. In addition, scientists have repeatedly linked estrogen-driven breast cancer with being overweight. Why? Fat cells produce lots of estrogen that fuels this type of breast cancer. In contrast, drugs (called aromatase inhibitors) that block fat cell estrogen can both decrease the recurrence rate of early breast cancer, and shrink metastases if the disease spreads.
At this point, one would be right to question why, if estrogen often propels the growth of breast cancer, it also can be used in its treatment. It is a paradox to be sure, one that had its beginning in the 1940s, when Sir Alexander Haddow, a brilliant Scottish chemist, first proposed that cancer-causing chemicals themselves might be effective to treat cancer.
Not only did his hypothesis prove to be correct (and became known as “The Haddow Effect”), it led scientists under his direction to discover a series of anti-cancer drugs, themselves carcinogens that are still in clinical use today.
One carcinogen pegged by Haddow as a possible breast cancer treatment was the synthetic estrogen, diethylstilbestrol (DES). Once again he was right. Although the drug was often toxic at the high doses required to be effective, and worked only about one-third of the time, for the next quarter-century it was widely used to shrink advanced breast cancer in post-menopausal women. The “estrogen paradox” was evident even then!
When tamoxifen (itself a weak estrogen that can cause uterine cancer) proved almost as effective as, but significantly less toxic than, DES, it became the drug of choice in the 1980s. DES was ultimately banned in most countries after it was linked to reproductive tract abnormalities, including vaginal cancer in young girls whose mothers took it in pregnancy to decrease the risk of bleeding, premature labour and miscarriage.
Despite the demise of DES, natural estrogens, such as estradiol (contained in Premarin, for example), continue to be approved for use in treating inoperable breast cancer. However, in the “modern era” they have been rarely prescribed for this purpose.
Now, with the just-published study in JAMA, that is almost certain to change.
The study’s rationale stemmed from earlier laboratory experiments with cultured breast cancer cells that could grow in the absence of estrogen (mimicking resistance to treatment with an aromatase inhibitor). It was found that when small amounts of estradiol were now added to the culture medium, the cells died.
To determine whether these findings might carry over to the clinic, oncologists assessed the effect of high (30 mg) and low (6 mg) daily doses of estradiol on the growth of estrogen-dependent breast cancer in 66 women whose disease had stopped responding to aromatase inhibitor drugs. Consistent with the previous experience with DES, 9 of 32 women responded to high-dose estradiol. What may not have been anticipated, but in keeping with the preceding lab data, an equal number of women (10 of 34) responded to low-dose estradiol, and with significantly fewer side-effects. As a result, low-dose estradiol will be adopted for future studies.
The study additionally found that positron emission tomography (PET) body scans performed twenty-four hours after the first dose of estradiol were highly predictive. Only patients in whom the PET scan detected increased glucose (sugar) metabolism in the tumours (a sign of early growth-stimulation) responded to treatment. In other words, an early stimulation of tumour cells by estradiol was soon followed by the reverse effect (shrinkage or stability of the cancer). A paradox, indeed.
Finally, there was one more bit of icing on the cake: two of seven women regained a response to their previous aromatase inhibitor after the estradiol improvement wore off.
 While the study was relatively small and the findings preliminary, I think it is likely that they will quickly change how oncologists treat late-stage estrogen-dependent breast cancer. Since generic estradiol is commercially available and already approved in breast cancer, oncologists can easily prescribe the 6 mg daily dose to women who stop responding to aromatase inhibitors. Moreover, a PET scan performed one day after the first dose will quickly indicate who should continue and who should stop.
Maybe something is new under the sun after all!

A story in today's news about how to safely dispose of prescription pain killers, often only months or up to three years beyond their expiry dates, prompts me to re-post this blog I wrote for CTV.ca/health in 2011.













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​Drug expiry dates: Should you use outdated medicine?
July 8, 2011 11:04 by Dr. Lorne Brandes

A recent e-mail from a friend immediately “caught my eye” (the pun will be evident in a moment). He thought I would be interested in a 2002 article , entitled, “Do Medications Really Expire?” by writer, Richard Altschuler.
“Does the expiration date on a bottle of a medication mean anything? If a bottle of Tylenol, for example, says something like ‘Do not use after June 1998,’ and it is August 2002, should you take the Tylenol? Should you discard it? Can you get hurt if you take it? Will it simply have lost its potency and do you no good?” Altschuler asked.
“In other words, are drug manufacturers being honest with us when they put an expiration date on their medications, or is the practice of dating just another drug industry scam, to get us to buy new medications when the old ones that purportedly have ‘expired’ are still perfectly good?” he added.
I paused to reflect on those important questions. A few weeks earlier, my ophthalmologist had given me some sample eye drops. “According to the date on the box, they expired last month. Are you okay with that, or would you prefer that I write you a new prescription?” she asked. “I… think… I’m okay with the samples,” I replied hesitantly.
There followed a discussion about how it makes no sense that a drug with an expiry date of December 31st suddenly stops working on January 1st. Yet, as I left her office, thanking her for the free samples, I wondered whether I might be playing Russian Roulette with my eye pressures.
Now, based on the information in my friend’s e-mail, I suspect that I wasn’t.
To begin, Altschuler explains that drug expiry dates are not a money grab cooked up by Big Pharma, but rather, the result of a 1979 federal law, mandated by the FDA.
He goes on to explain, “…the expiration date… specifies only the date the manufacturer guarantees the full potency and safety of the drug - it does not mean how long the drug is actually ‘good’ or safe to use…. [M]edical authorities uniformly say it is safe to take drugs past their expiration date - no matter how ‘expired’ the drugs purportedly are. Except for possibly the rarest of exceptions, you won't get hurt and you certainly won't get killed.”
Perhaps not hurt or killed. But what about potency? How long do drugs, such as those eye drops, remain effective? Happily, a more recent publication goes a long way in answering that question.
According to a comprehensive 2006 paper, published in the Journal of Pharmaceutical Sciences by scientists at the FDA’s Center for Drug Evaluation, we now know quite a lot about the shelf-life of many pharmaceuticals, thanks to the American military. Why?
Because the U.S. Department of Defense (DoD) maintains a billion dollar stash of drugs (called the Strategic National Stockpile), including a host of antibiotics, anesthetics, narcotics, anti-allergics, anti-toxins, anti-malarials, anti-convulsants, vaccines and intravenous solutions. It’s part of the DoD’s Medical Readiness Strategic Plan for war or natural disasters.
But just like the everyday consumer, the DoD’s drugs have those same expiry dates. Replacing such a huge cache of unopened/unused drugs every 3 to 5 years is not only potentially wasteful, but hugely expensive for the taxpayer. Therefore to gain a handle on the question of drug stability, the DoD, in conjunction with the FDA has, for the last twenty years, monitored 122 of its drugs in a shelf life extension program, known by the acronym “SLEP”.
Here’s how it works, as described in the journal paper: “Certain lots of drug[s] that are approaching their labeled expiration date are selected… [and]… subjected to a battery of tests… If a lot fails any [original] specification…the shelf life for that lot is expired. [If a drug lot passes all the tests] and the [predicted] remaining expiration period is longer than 1 year, the [drug lot] is granted a new expiration date.”
What has the program found? Fully 88% of the 3000 drug lots tested have an average extended shelf-life of 5.5 years beyond the original expiry date! Indeed, many pills, powders and liquids have been found to be stable for an extra ten or more years, while only 10 of the 122 drugs failed to gain an extension beyond their original expiry date. Even in those cases, the drug lots often failed for reasons other than loss of potency, such as a change in appearance.
So what do I advise? Extrapolating from the SLEP findings, if an unopened medication, such as my ophthalmologist’s eye drop samples, are stored according to the manufacturer’s recommendations, they should retain their safety and effectiveness for a year or more beyond their expiry date. Opened eye drops, on the other hand, should be discarded after a month or two, not necessarily because of a decrease in potency, but because of concern over bacterial contamination , especially at room temperature.
As for the majority of opened prescriptions and over the counter medications, such as aspirin, Tylenol, antibiotic pills or capsules, blood pressure pills, antihistamines and acid blockers, it is very likely that they, too, will remain safe and effective for months or even years beyond their expiry date if stored properly in a closed container.
However, there is one important exception: if any drug falls into the category of “lifesaving”, its expiry date should be heeded irrespective of any potential for a longer shelf life. In serious disease situations, no one should take a chance with the effectiveness of their medication!
 
 

This week, a story appeared on CTV news about the failure of Health Canada to regulate cosmetics containing potentially dangerous ingredients. Here is a a blog I wrote on that subject in 2009.













Skin care products and cancer: What manufacturers don’t tell you
October 14, 2009 11:15 by Dr. Lorne Brandes
 
On a recent visit to a department store cosmetics counter, I was amazed at the number and variety of “rejuvenating” skin creams and lotions for sale -- and not just for women!
“How much did all that cost?” I asked warily as the smiling clerk handed the Visa card back to my wife.
“If they help my skin look younger, it’s worth it,” was all she would say.
It now appears that her faith in the products she bought may have been misplaced: a new report in the Journal of Clinical Oncology (JCO) warns that an ingredient in some skin creams may have serious long-term health consequences for women with, or at risk for, breast and uterine cancer. The offending substance? Estrogen!
The story began with an alert oncologist. He observed that the skin of a woman he was treating for estrogen-driven breast cancer looked more youthful since her previous visit. The doctor quickly ascertained that, starting four weeks earlier, his patient had been applying a new moisturizing skin cream after her daily bath.
His interest was immediately piqued. For years, it has been known that one of the benefits of taking estrogen for relief of menopausal symptoms is younger-looking skin. Could the cream she was putting on her skin contain estrogen? The product information provided no indication that it did.
His suspicion aroused, the oncologist sent a sample of the patient’s skin moisturizer, along with 15 other skin products, to an independent lab for analysis. The price of the creams ranged from $10 to several hundred dollars. Each was chosen based on the manufacturer’s claim that it rejuvenated, or enhanced the youthful appearance, of the skin. None listed estrogen as an ingredient.
The results supported the doctor’s concern: six -- almost 40 per cent -- of the creams contained significant amounts (up to 0.61%) of estriol or estrone, two potent forms of estrogen. As a comparator, Estrase, a vaginal cream prescribed to treat symptoms of vaginal dryness in post-menopausal women, contains up to 60 times less estrogen!
In publishing these results, it was decided not to provide the brand names of the estrogen-containing creams. While I suspect that the authors (or the journal’s editors) may have been concerned about potential lawsuits, an alternative reason was given: “…since cosmetic companies frequently change their formulations, contents of each product may not currently be similar to those obtained [at the time of analysis, in April 2007].”
Cosmetic companies are not currently required to submit their products for regulatory approval to agencies such as the FDA or Health Canada. Rather, as noted in a recent scientific review, complex skin formulations that contain potentially harmful ingredients are largely regulated by the cosmetic manufacturers themselves. And, as we have just learned, these same manufacturers generally do not feel inclined to divulge the presence of “problematical” ingredients like female hormones.
Should we be worried about the estrogen content of facial creams and other skin care products? In short, yes.
While skin absorption of ingredients in topically-applied creams and lotions can vary depending on the formulation and length of exposure, one extreme example has been published. A 93-year-old woman, who had applied an estrogen-containing cream to her skin for seven decades went to her doctor with uterine bleeding and a breast lump. She was found to have a uterus “as large as that of a normal adult menstruating woman,” while the breast lump proved to be malignant. The authors believed that both findings were likely related to prolonged use of the skin cream.
More to the point, women with breast cancer who are under treatment with an estrogen-lowering aromatase inhibitor should be especially concerned about any product that, without their knowing it, could work against this treatment by raising the level of blood estrogen through the skin. Similarly, healthy women at risk for breast or uterine cancer should also beware of the increased exposure to environmental estrogen inherent in some rejuvenating skin preparations.
To quote the authors of the JCO report, “We believe that women, especially patients with a history of breast cancer, should be able to understand the potential risks when exposed to estrogenically active molecules in commercially available topical moisturizers. Because our testing methodology was only intended as a screening process, we strongly encourage the scientific community and the U.S. Food and Drug Administration to repeat and expand on the results of these screening tests.”
I agree. And in light of a new warning just issued by noted scientist, Dr. Samuel Epstein, on the potential cancer-causing hormonal agents in cosmetics, their recommendation for FDA involvement is well-justified.