Drugs for Cancer Prevention – NY Times Misses the Point

In yet another article addressing the war on cancer, The New York Times today tackles cancer prevention, focusing on alternative and mainstream Pharma products marketed to reduce the risk for cancer.

While author Gina Kolata seems to have done her homework when it comes to the failure of alternative medicine to prevent cancer, she has missed the story completely when it comes to telling why the medical profession and patients may have failed to embrace Big Pharma’s push to use their drugs to prevent breast and prostate cancer. Of course, that’s not surprising since almost exclusively, the experts she interviewed were those who conducted the clinical trials of these drugs.

Since I’m not a urologist, I’m not going to comment on the use of finasteride to prevent prostate cancer, except to point out that the one expert quoted in favor of its use has served as a consultant to Merck and AstraZeneca, both of whom make the drug, while the other works for Astra Zeneca.

So let’s talk about tamoxifen and raloxifene, two drugs that are approved for the prevention of breast cancer.

Tamoxifen and Raloxifene

The maker of Evista (raloxifene) is targeting both docs and women, urging them to calculate their lifetime risk for breast cancer and consider taking the drug if that risk for breast cancer is increased. Since raloxifene is also approved for treatment of osteoporosis, the drug makers are selling it as a two for one.

Both tamoxifen and raloxifene cut the risk for breast cancer in half among high risk women who use the drug for 5 years. Tamoxifen also prevents DCIS and LCIS in addition to invasive cancer, while raloxifene does not reduce these risks.

But, Tamoxifen can cause uterine cancers. The risk is low, about 1 in 500, but includes uterine sarcomas, a particularly aggressive tumor, and may persist even after the drug is discontinued. There is no screening for uterine cancer in tamoxifen users – ultrasound is useless, since the endometrium very frequently appears abnormal even if there is no cancer. We docs are left telling women just to tell us if they blee

Now, for women who are taking tamoxifen for treatment of breast cancer, the risk for uterine cancer is almost always outweighed by the benefits in terms of cancer treatment. But for woman who have never had (and may never get) a breast cancer, the uterine cancer risk is a deal breaker, especially when she asks what I can do to screen her and I tell her “nothing”. I can quantify it for her – look, your risk for breast cancer will be reduced from 20% to 10%, I might say – and your risk for uterine cancer increased by less than one percent.

Okay, I’m interested, she might say. So tell me – Are there any other risks?

Yes, I’ll say.

Both raloxifene and tamoxifen carry an increased risk of thromboembolism. According to the package insert for Evista (raloxifene), DVT occurred in 1 out of every 100 women using the drug for an average of 2.6 yrs, over twice the rate for placebo users. Fatal stroke risk was about 1.5 times higher in Evista compared to placebo users, though that risk was concentrated in postmenopausal women at increased risk. Unfortunately, nowhere in the marketing materials for Evista is there a risk calculator that helps me or my patients assess their personal risk for these complications from the drug.

So, I’ll fudge it. Now my risk calculation for this patient looks something like this – Breast cancer, lowered from 20% to 10%. Uterine cancer, increased by 0.2%, but no screening. Blood clot risk = 1%. Fatal stroke risk = 0.3% over 5 yrs if you have risk factors, miniscule if you don’t.

Okay, she’ll ask me. How is it going to make me feel?

Probably fine, I say, but there are some side effects that might bother you, the most common of which is hot flashes in about 10% of users. Some women experience joint pains and leg cramps as well. These symptoms can occasionally be severe, although only about 1% of users stopped the drug because of hot flashes in the clinical trials. And most women will notice an increase in vaginal mucus that, as a gynecologist, I don’t have concerns about. Not uncommonly, my patient will have had a friend who has experienced a bothersome side effects from taking Tamoxifen. That’s usually the kiss of death for any drug – a girlfriend with a side effect…

And oh yeah, there’s also the increased risk for cataracts with Tamoxifen, but not raloxifene.

Now, if a woman has osteoporosis, I can add that to the plus side of the balance scale for raloxifene use. Now I’ve got to do her risk for fracture based on her bone density and talk to her about the other options she may have to treat her osteoporosis as well.

Is anyone really wondering why we docs and our patients haven’t jumped onto Big Pharma’s cancer prevention bandwagon? We’re asking patients to balance competing statistical risks for conditions she may never get, in return for a benefit she may never need.

I do prescribe raloxifene it for treatment of osteoporosis, and if there is a strong family history of breast cancer, I may even try to steer my osteoporotic patients who are not at increased risk for clots towards using it. However, it is the rare patient who chooses this drug over a bisphosphonate such as Fosamax and Actonel when I inform her of the risks and benefits of both these classes of drugs. Even patients with strong family histories of breast cancer just don’t want the potential side effects of a drug in return for a reduced risks for a cancer they may never get.

Hello – Birth Control Pills?

Kolata completely misses out on the fact that millions of women are already taking a pill that reduces their risk for cancer – the birth control pill. It cuts ovarian cancer by up to 80% and endometrial cancer by almost half.

Like Tamoxifen and Raloxifene, the pill carries an increased risk of blood clots, a trade off many women are willing to make in return for prevention of pregnancy, which itself carries an even higher risk of clotting. Not to mention the benefits the pill can confer for women with menstrual disorders such as dysmenorrhea, menorrhagia, endometriosis and its efficacy in treating acne and even PMS. For most healthy young women, the balance of benefits and risks of pill use is favorable, even before considering the cancer prevention aspects of the p

For the record, I inform each and very patient who starts estrogen containing birth control that there is an increased risks of clots. I quantify it for them, tell them that it is a real risk and give them strategies they can use to minimize these risks. Surprisingly, that discussion has rarely deterred a patient from starting on hormonal birth control. It may be that pill patients are younger and feel more invincible than the older women being targeted by the makers of Evista. But I think most of them are actually weighing their risks of pregnancy against the risks of blood clots, comparing this to their perceived downsides of barrier methods and/or the IUD, and coming out on the side of using the pill.

Prevention is the holy grail for Big Pharma

Let’s face it – an indication for prevention of a disease grows the potential market of a drug by millions. But if you’re going to market a drug to healthy individuals, it better be free of risk or have some other benefit that patients can see right away.

Otherwise, it just ain’t gonna’ sell.

Which probably explains why Kolata tells the story of the cancer prevention challenge as though it were a failed pharmaceutical marketing campaign. Missing from her article, unfortunately, is the question that asks whether pharmaceuticals are really the right strategy to prevent cancer. Or that asks if we really mean to ask 100% of men over 50 to take a drug to prevent prostate cancer, when, in the same breath, we are telling them we should stop screening for it? Or whether 100% of women over 60 take a drug that increases their risk for thromboembolism and uterine cancer so that 20% of them won’t get breast cancers that some are suggesting may regress or be so indolent that they will die of something else before it kills them?

Of course, we could just sell them another drug to lower their clotting risks..