Category Archives: oncology

Why don’t we just put statins in the water supply and be done with it?

Statins and the risk of colorectal cancer in last week’s NEJM is a case-control study from Israel that looked at about 2000 patients with colorectal cancer and a similar number of controls, and found that “the use of statins for at least five years (vs. the nonuse of statins) was associated with a significantly reduced relative risk of colorectal cancer”. The odds ratio was about 0.50.

At the risk of sounding like a broken record, this is yet another case-control study, useful as hypothesis generating, but not much else. The authors performed their analysis adjusting for multiple co-variates, such as aspirin use, vegetable consumption, red-meat consumption, but there is no way they can sufficiently adjust for all variables to convince me.

For one thing, they don’t mention adjusting for low-saturated fat diets which patients who take statins are likely to adhere to. And there are sure to be other confounders associated with statin treatment.

The one fact that almost convinced me was that the authors found no protective effect from non-statin cholesterol lowering agents (fibrates). These are likely to be associated with most of the same confounders as statins. BUT, there were only 20 patients taking these drugs, too few to be statistically reassuring, and the reason for prescribing a fibrate rather than a statin is more likely to be hypertriglyceridemia than hypercholesterolemia, implying a different population and perhaps a different diet as well.

Medpundit is also critical of this study. I have to disagree with her main argument against it, however. She feels that the biggest flaw is that the two groups were not matched for ethnicity, with a higher percentage of Ashkenazi Jews in the cancer group. However, in their adjusted analysis, the authors specifically state that they adjusted for ethnicity. In my opinion, the biggest problem with case-control studies is not that they do not adequately adjust for known confounders, but rather that they don’t take into account confounders they have not thought of.

MRI for breast imaging

Last week’s JAMA had an article on magnetic resonance imaging of the breast prior to biopsy, which evaluated the performance of MRI imaging in evaluating patients with breast abnormalities. This study found that MRI had good sensitivity but only moderate specificity for detecting cancer. The negative predictive value of MRI was only about 85%, not high enough to obviate the need for biopsy.

In the same issue is an excellent editorial by Monica Morrow from Fox Chase Cancer Center in Philadelphia, Magnetic resonance imaging in breast cancer — one step forward, two steps back?

Dr. Morrow discusses the role of MR imaging of the breast. She notes that at present there are two main scenarios in which MRI is being used: for the screening of women at high risk for breast cancer, and for supplemental evaluation of patients with abnormalities of the breast.

The screening of women at high risk, such as those with BRCA mutations, lends itself to MRI evaluation, because these women are often younger, with denser breast tissue, a situation where MRI has an advantage over conventional mammography.

On the other hand, using MRI to evaluate patients with breast abnormalities (clinical and/or mammographic) is a different matter. As demonstrated in the study, the specificity and negative predictive value of MRI are not sufficient to allow the avoidance of breast biopsy. Nevertheless, MRI is being used more and more in this context. Why? Because of the perception that it is more sensitive and can pick up multicentric lesions better than mammography. Thus, it can be used to make decisions about the appropriateness of local (breast-sparing) treatment.

Here, Dr. Morrow makes an interesting point. Although MRI can pick up multicentric cancers with greater sensitivity than mammography, she argues that the need for mastectomy in these cases is not clear. She draws a parallel to the 1970’s, when breast-sparing surgery was being investigated. At that time, pathologic studies indicated that breast cancer was often multicentric; this was used to argue against the advisability of limited surgery. However, clinical trials showed that as long as the surgical margins were clean, breast-sparing surgery plus radiation of the breast yielded excellent results. Analogously, the detection of multicentric cancers by MRI may push towards mastectomy, but without clinical trials it isn’t clear that this will yield better results.

Breast cancer is out of my area of expertise, but this editorial was short, easy to read and thought-provoking.

The situation Dr. Morrow describes reminds me a bit of a recent development in cardiology, the advent of non-invasive methods for visualizing coronary arteries (CT angiography). Visual evidence is very convincing, and there is a strong urge to act upon what we see. Paradoxically, the ability to visualize coronaries non-invasively may well increase the number of invasive procedures, as the instinct to open up tight lesions will be hard to resist. Whether this will always be the right thing to do is another question.

In both cases, seeing is believing, but belief isn’t always the best basis for action in medicine.