Considering Aromasin for Healthy Women, and the New Breast Cancer Prevention Study
I’m minding the annual meeting of the American Society of Clinical Oncology from a distance this year.
So far, the big breast cancer story syncs with a NEJM paper published yesterday on-line, on the use of exemestane (brand name: Aromasin, manufactured by Pfizer) to prevent invasive breast cancer. These patent-protected pills block the body’s normal production of estrogen.
The main finding was that for women deemed “at risk” for developing BC – as defined by the investigators – the incidence of cancer was significantly reduced when they took Aromasin as compared to a placebo. At a median observation point of 35 months, there was no observed effect on the women’s survival.
What’s right about the study: it’s prospective, randomized and large, including over 4560 women. The results are clear in terms of percents and relative risks: There was a 65% relative reduction in the annual incidence of invasive breast cancer (0.19% vs. 0.55%) and a hazard ratio of 0.35 (with confidence interval 0.18 to 0.70; P=0.002). So they’ve got strong stats.
Estrogen, typically depleted but not absent in post-menopausal women, can promote growth of breast cancer cells. From the paper’s first section: “Aromatase inhibitors profoundly suppress estrogen levels in postmenopausal women and inhibit the development of breast cancer in laboratory models.” So the findings are plausible, which helps, too.
The first problem (or non-problem, really) is there were only 43 cases of invasive BC in total; there wasn’t much cancer, or its reduction, in either arm of the study in terms of absolute numbers. This makes the divergent percents reported seem far less impressive. Second, and more importantly – the long-term consequences of taking this relatively new estrogen-inhibiting drug, in terms of women having thinner bones, possibly more cardiovascular disease, diminished libido and other side effects, are unknown.
Already there are two drugs marketed to prevent breast cancer in some women: tamoxifen and raloxifene. These drugs, also anti-estrogens, have significant side effects including blood clots, and few women choose to take them as prophylaxis for breast cancer. The new study suggests Aromasin is better because it’s got fewer side effects; Pfizer’s idea is that it’s a safer option for women who want to reduce their risk of developing BC.
But what caught my attention is who qualified for this trial: Most healthy women over the age of 60 – that’s a whopping, growing population of potential Aromasin-takers, besides the relatively small number of women with known pathology such as precancerous or stage 0 breast cancer (conditions like LCIS and DCIS, for which a preventive drug seems justifiable) or high risk-conferring BRCA-1 or -2 mutations.
Reading over the trial’s eligibility, I had to wonder, how could anyone think it reasonable to treat all women over the age of 60 with an estrogen inhibitor? And who populated the IRBs that approved this protocol? (Imagine if oncologists were to propose testing the effects of chemical castration in thousands of men over the age of 60; few would support such a trial, although in all likelihood androgen ablation would reduce the incidence of prostate cancer in men.)
The NEJM article lists support for the work from the Canadian Cancer Society Research Institute, the Canadian Institutes for Health Research, Pfizer, and the Avon Foundation. Among my many questions, I’d like to know what exactly what fraction of the study’s support came from Pfizer. The Journal (and every) should break this down for a published non-advertisement: If Pfizer provided 5% or 50% or 95% of funding for the trial, readers should be informed, as should women who might choose to take this drug and their doctors who might prescribe it.