Go ahead and eat grapefruit

American women fear breast cancer more than heart disease, according to most studies, even though heart disease is responsible for 10 times as many female deaths every year -- and heart disease deaths exceed breast cancer deaths in every decade of a woman’s life.

Of women who are diagnosed early with breast cancer, more than 90% will survive, and most will not need disfiguring mastectomies or even chemotherapy. But the media understand how deeply women fear breast cancer, and the result is that every study that seems to find a link between some new risk factor and the disease makes headlines everywhere, captures public attention and stimulates the blogosphere into overdrive.

Grapefruit is the most recent culprit. According to a study in the Journal of the American Medical Assn., eating a quarter of a grapefruit a day increases the risk of breast cancer by 30%. For many women, grapefruit immediately was toast.

To assess these studies for their real-life implications, let alone for making decisions about our own behavior, the public needs to understand the difference between absolute risk and relative risk. If we tell you that the relative risk of breast cancer is increased by 300% in women who eat a bagel every morning -- Relax! It’s not! -- that sounds alarming, but it is not informative. You would need to know the absolute numbers of bagel-eating breast cancer patients. If the number shifted from one in 1,000 women to three in 1,000 women, that is a 300% increase, but it’s meaningless. If the risk had jumped from 100 women to 300, we might reasonably be concerned.

In the large epidemiological studies that generally include tens of thousands of people, it is very easy to find a small relationship that may be considered “significant” by statistical convention but that, in practical terms, means little or nothing. For example, in July 2002, the Women’s Health Initiative reported a 26% increase in breast cancer risk for women on hormone replacement therapy, which sounded worrisome. Even if that number were statistically significant -- and it was not, by the way -- this is what it translates into: The risk of breast cancer would increase within the studied population from five in 100 women to six in 100 women.

We now have a fat file folder of all the studies we could find that have reported an association between some purported risk factor and breast cancer. Of these, the ones that got the most attention were three Women’s Health Initiative reports. In 2002, investigators found an increased relative risk of 26% from using combined estrogen and progesterone; in 2003, it was 24%; and in 2004, the relative risk from using estrogen alone was minus 23% (suggesting it was protective against breast cancer).

To put those findings in perspective, consider these published studies showing the increased relative risk of breast cancer from:

* eating fish: 14%

* eating a quarter of a grapefruit a day: 30%

* gaining more than 33 pounds in pregnancy: 61%

* being a Finnish flight attendant: 87%

* being a Dutch survivor of childhood famine: 201%

* using antibiotics: 207%

* having a diagnostic chest X-ray: 219%

* being an Icelandic flight attendant: 410%

* using an electric blanket: 630% (but only if you are a black woman who used it for more than 10 years but less than six months in a given year).

Why was there no call for Icelandic flight attendants to quit (or transfer to Lufthansa), for black women to use electric blankets for more than six months a year but only for nine years, for labeling antibiotics as carcinogens? Because these findings, which were improbable to begin with, were never replicated. In contrast, the increased relative risk of lung cancer from smoking is consistently between 2,000% and 3,000%. That’s a finding that means something.

Unfortunately, good news doesn’t travel as fast as fear does. In 2006, the Women’s Health Initiative investigators reanalyzed their data and found that the risk of breast cancer among women who had been randomly assigned to take hormone replacement therapy was no longer significant. Women assigned to take a placebo but who had used hormone replacement therapy in the past actually had a lower rate of breast cancer than women who had never taken hormones.

This reassuring but non-scary news did not make headlines. Neither did the real findings from the March 2008 Women’s Health Initiative report, which followed women in the sample who had stopped taking hormones for the previous three years. The researchers reported that the risk of cardiovascular events, malignancies, breast cancers and deaths from all causes was higher in the hormone-replacement-therapy group than in the placebo group even three years after stopping the therapy -- pretty alarming. But when we read the article closely, we saw that not one of the associations between hormone replacement therapy and breast cancer, or between the therapy and mortality rates from any cause, was statistically significant. Unfortunately, this did not stop the investigators from highlighting their negative findings as meaningful and troubling, and that is what most of the media picked up.

No wonder the public, assaulted by numbers and frightening headlines, alternates between panic and cynicism. Physicist Richard Feynman once said, “If something is true, really so, if you continue observations and improve the effectiveness of the observations, the effects stand out more obviously, not less obviously.”

The association between hormone replacement therapy and breast cancer becomes less obvious with every study. We all want to understand the risk factors in breast cancer that are “really so,” but to do that, we have to give up entrenched beliefs when the data do not support them, and look elsewhere. In the meantime, enjoy your grapefruit.