May 31, 2007

You Don’t “Beat” Cancer in Mere Months

The only claim more medically ridiculous than a Lindsay Lohan or a Britney Spears announcing defeat over substance abuse after a month-long stint in rehab is the claim of a Farrah Fawcett, Sheryl Crow, or Melissa Etheridge that she has “beaten” cancer after a few months of treatment. “Three months after being declared cancer-free, she copes with the unexpected return of her illness”, rang out the June 4 People magazine, referring to the unfortunate former Charlie’s Angel, Fawcett. I doubt any oncologist would have made that statement.

Five-Year Survival
Even the 5-year survival statistic used by the National Cancer Institute that seems to have eluded the cancer celebrities ignores the micrometastases that can persist, no matter how targeted or toxic the treatment or how dramatically symptoms have abated. My mother passed the magical 5-year mark, yet her breast cancer returned at year 17. I had thyroid cancer in 1993, and I know it isn’t and never really will be entirely gone. Even people whose leukemia appears to have vanished following treatment with Gleevec – the closest thing to a “miracle” drug I’ve ever heard of – can still have, at the RNA level, traces of something not quite right. They can feel fine, their blood can look normal, even their telltale mixed up chromosomes can be undetectable, yet the errant oncoprotein that lies behind the disease is, sometimes, still there. That’s why when people go off Gleevec, such as to become pregnant, a supposedly vanquished cancer can return.

Five-year survival rates assess the deadliness of a cancer on a population level. By “survival”, the definition means anyone still alive, whether or not symptoms and/or treatment are ongoing. Such a population statistic should not be applied to an individual case. Yet I just received a phone call from a Red Cross representative seeking a donation. When I declined, explaining my cancer history, to my utter astonishment she asked me if it had been more than 5 years since my diagnosis. Not wishing to launch into a spirited discussion of the concept of micrometastases, I politely declined, explaining that I would sooner donate bovine blood than mine, in which a cancer cell or two is bound to lurk.

With thoughts of the Red Cross and poor Farrah in my mind, I checked out the Red Cross website. Lo and behold, as of their May 24 update of the eligibility guidelines, besides the obvious blood-borne cancers, “Other types of cancer are acceptable, if the cancer has been treated successfully, and it has been at least 5 years since treatment was completed and there has been no cancer recurrence in this time.”

Enter Gene Expression Profiling
Whoa! Hasn’t anyone at the Red Cross heard about MammaPrint, the test that the FDA approved earlier this year (Buyse 2006)? It’s the first test that detects a gene expression signature – rather than mutations – that is correlated with risk of recurrence 5 to 10 years from diagnosis! It’s based on 70 genes and has been marketed in Amsterdam, where it was developed, since 2005.

Do the math: If MammaPrint predicts increased risk of cancer resurfacing after 5 years, why is the Red Cross accepting blood from people who’ve had cancer just because they have passed the 5-year population-based mark? I understand that individual donation decisions are made at the collection sites based on a person’s detailed family history, but if there’s still doubt – and in science there always is – why risk letting cancer cells get into the blood supply?

The idea that tumors can return isn’t new. In 1889 English surgeon Stephen Paget meticulously traced the spread of disease from the breast to secondary organs in 735 women, calling the original tumor the “seed” and the site of spread the “soil” (Paget 1889, Fidler 2003). The new twist today, akin to a crystal ball, is the gene expression profiling that is the basis of MammaPrint – the first genetic peek into Paget’s timeless seed and soil hypothesis. Still in development are a 5-gene signature that predicts survival in non-small-cell lung cancer (Chen 2007), and another that foretells whether breast cancer will spread to the lung or bone (Gupta 2007).

Many such prognostic tests are in the works. And so cancer diagnosis circa 2015, or even sooner, will come with predictions not only of where and when the disease is most likely to spread, but also which drugs will be most effective, with the fewest side effects. The ability of gene expression profiling to highlight molecular derangements not apparent at the cellular level will take cancer diagnosis and prognosis to a new level.

But back to practicality and stars who miraculously beat cancer in weeks. I prefer Elizabeth Edwards’ stoic recognition of her cancer as a chronic, treatable condition than the giddily premature proclamations of having escaped the oncobullet.

It takes time to come to terms with cancer. You learn to live with the vestige of the disease, for it may remain, even if you are in perfect health. Perhaps most micrometastases never translate into clinical recurrences. We outlive our cancers. I read somewhere that having cancer divides time, so that your remaining days, whether they are few or many, are different. It’s trite, but oh so true.

I’m not trying to throw cold water on all the people who have fought so bravely and endured the indescribable fear of knowing that cells are dividing out-of-control in the body. I had only a tiny taste of that terror. But what bothers me about the celebrities who claim to have “beaten” cancer after a few months of treatment, besides raising false hopes, is the implication or outright claim -- often the fault of the media -- that they “did everything right”.

What does that say about the rest of us, like me, who avoided tobacco and sunburns, stuffed ourselves with broccoli, exercised like crazy, and got cancer anyway? Alas, for many of us, cancer just happens. It is a consequence of somatic mutations, which are a consequence of occasionally faulty DNA replication and repair.

So Farrah, Sheryl, and Melissa, I love you all, I wish you well, but please be careful not to proclaim your triumph over the devil that is cancer after only a few months. Unfortunately, millions of us know better.

- Contributing Editor Ricki Lewis

Buyse, M., et al. 2006. Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. Journal of the National Cancer Institute 98:1183-1192.

Chen, H-Y, et al. January 4, 2007. A five-gene signature and clinical outcome in non-small-cell lung cancer. The New England Journal of Medicine 356(1):11-20.

Fidler, I.J. 2003. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nature Reviews Cancer 3(6):453-458.

Gupta, G.P., D. X. Nguyen, A.C. Chiang, P.D. Bos, J.Y. Kim, C. Nadal, R.R. Gomis, K. Manova-Todorova, and J. Massague. April 12, 2007. Mediators of vascular remodeling co-opted for sequential steps in lung metastasis. Nature 446:765-770.

Paget, S. 1889. The distribution of secondary growth in cancer of the breast. The Lancet 133(3421):571-573.

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