A while back I wrote about rethinking how we screen for breast cancer using mammography. Basically, the USPSTF, an independent panel of physicians and health experts that makes nonbinding recommendations for the government on various health issues, reevaluated the evidence for routine screening mammography and concluded that for women at normal risk for breast cancer, mammography before age 50 should not be recommended routinely and should be ordered on an individualized basis, and that routine formalized breast self-examination (BSE) should also not be routinely recommended. In addition, for women over 50, it was recommended that they undergo mammography every other year, rather than every year. These recommendations were based on a review of the literature, including newer studies.

To say that these new recommendations caused a firestorm in the breast cancer world is an understatement. The USPSTF was accused of misogyny; opponents of health care reform leapt on them as evidence that President Obama really is preparing “death panels”; and HHS secretary Kathleen Sebelius couldn’t run away from the guidelines fast enough. Meanwhile, a society I belong to (the American Society of Breast Surgeons) issued a press release accusing the USPSTF of sending us back to the “pre-mammography” days when, presumably women only found breast cancer after it had grown to huge size (just like Europe and Canada, I guess, given that the recommendations for screening there closely mirrors those recommended by the USPSTF). Meanwhile, in the most blatant example of protecting its turf I’ve seen in a very long time, the American College of Radiology went full mental jacket with a press release that was as biased as it was insulting. Meanwhile some physicians even likened the recommendations to going back to being like Africa, Southeast Asia and China as far as breast screening goes in that he actually speculated that he’d now become very busy treating advanced, neglected breast cancers. Unfortunately, as Val pointed out, the communication of the USPSTF guidelines to the public was almost a perfect case study in how not to do it. Even though the science was in general sound and the USPSTF recommendations were in essence close to identical to what other industrialized nations do, they were communicated in just such a way as to produce maximum misunderstanding and misuse for political purposes.

Despite all the hysterical and in some cases disingenuous attacks on the new guidelines, there is one criticism that actually resonates with me because I work at a cancer center in a very urban environment with a large population of African-American women. Last week I heard on NPR this story:

Many African-American women don’t fit the profile of the average American woman who gets breast cancer. For them, putting off the first mammogram until 50 — as recommended by a government task force — could put their life in danger.

“One size doesn’t fit all,” says Lovell Jones, director of the Center for Research on Minority health at Houston’s M.D. Anderson Cancer Center. Jones says the guidelines recently put out by the U.S. Preventive Services Task Force covered a broad segment of American women based on the data available. “Unfortunately,” he says, “the data on African-Americans, Hispanics and to some extent Asian-Americans is limited.”

So while the recommendations may be appropriate for the general population, he says, it could have a deleterious affect on African-American women who appear to have a higher risk of developing very deadly breast cancers at early in life.

And this is actually true. Some of the studies used to develop the latest mammographic guidelines were performed in Scandanavian countries, and in the others arguably African-American women were underrepresented. As the article points out:

When you look at the death statistics for breast cancer in African-American women and compare them to white women, it’s stunning. Beginning in their 20s, into their 50s, black women are twice as likely to die of breast cancer as white women who have breast cancer. In older black women, cases of breast cancer decline, but the high death rates persist.

Overall, breast cancer deaths have been declining for nearly a decade (by 2 percent annually), yet deaths of African-American women have been dropping at a much slower pace. In 2009, an estimated 40,170 women will die from breast cancer. Nearly 6,000 will be African-American women.

Why this disparity exists is unclear. One potential reason is that, for whatever reason, African-American women tend to develop a more aggressive form of breast cancer known as “triple negative” cancer. What triple negative means is that the tumor is estrogen receptor negative [ER(-)], progesterone receptor negative [PR(-)], and HER2/neu negative [HER2/neu(-)]. The lack of estrogen receptor means that these tumors don’t respond to antiestrogen drugs, while the lack of HER2/neu means that they don’t respond to Herceptin. In other words, there are no targeted therapies for these tumors, only cytotoxic chemotherapy or nothing.

More importantly, there is something about the biology of these tumors that makes them more aggressive. They may respond well initially to chemotherapy but they tend to relapse rapidly and kill quickly. This subtype of tumor generally makes up around 15% of cancers among women who are not black, but among African Americans it makes up nearly 40% of tumors. This is a striking difference, and five year survival for women with triple negative cancer is considerably lower than for other types of breast cancer, particularly for young, premenopausal African-American women.

With that background, it’s not unreasonable to ask what “normal” risk for breast cancer is for purposes of recommending a program of screening mammography. On the one hand, if young African-American women are at a higher risk for breast cancer, then beginning their screening at an earlier age makes sense because it is the lower risk of breast cancer in women in their 40s that led the USPSTF to conclude that the risk-benefit ratio of mammography was less favorable in this age range. On the other hand, the more aggressive nature of breast cancer in young, premenopausal African-American women means that length bias becomes a consideration. Basically, length bias means that mammographic screening tends preferentially to pick up slower-growing, more indolent tumors. Faster-growing, more aggressive tumors tend to “pop up” between screening intervals. So, even if screening were started earlier for African-American women, it’s not clear that the benefits would be as dramatic as we might hope. Indeed, the NPR story alludes to this:

Sheppard even wonders if the old guideline of routine screening every year beginning at age 40 is good enough. “The tumors are growing fast and the intervals that we prescribe may not work,” she says. “How can we have better diagnostic tools, better screening tools that can capture the women that aren’t the average woman?”

A blogger going by the pseudonym of Isis the Scientist brought up this very issue the other day has a point when she wonders:

The other thing I wonder about is the effect these recommendations will have on the perception of health care equity. A black woman is more likely to develop aggressive cancer than a white woman before age 50, yet the USPSTF has recommended not to actively screen women less than. I wonder how this will be interpreted by that community? Black women experience a distrust of scientists performing clinical trials (second reference here), operate within a healthcare that is not always sensitive to their needs, and use mammography as a resource less frequently than white women. Will these new recommendations foster feelings of distrust and reinforce the notion that the current health care system does not adequately meet their needs?

There is a legitimate concern that the USPSTF guidelines may not be a good fit to African-American women because not only do they tend to have more aggressive disease at a younger age but they have been underrepresented in many of the large screening trials that have been used to formulate the recommended mammography guidelines. For that reason, upon further reflection I don’t think that the USPSTF guidelines should be used to determine how and when African-American women should undergo screening, as I consider them to be at a high enough risk that screening beginning at 40 makes sense.

However, as much as she did raise a valid point when she questioned whether the current mammography guidelines should apply to African-American women, still I must remonstrate with Isis and point out that the article by Nicholas Kristof that she cited in support of her speculations is dubious at best and a load of grade-A woo at worst. For example, Kristof states:

Dr. Philip Landrigan, the chairman of the department of preventive medicine at Mount Sinai, said that the risk that a 50-year-old white woman will develop breast cancer has soared to 12 percent today, from 1 percent in 1975. (Some of that is probably a result of better detection.)

What’s very important to realize is that 12% of women do not get invasive breast cancer as compared to 1% in the past. Moreover, “some of that” is not “probably” a result of better detection. Most of it is almost certainly a result of better detection of earlier breast cancer, including pre-invasive lesions like ductal carcinoma in situ (DCIS), through widespread mammography screening programs. Indeed, as this report by the American Cancer Society shows, the incidence of invasive breast cancer per 100,000 women is not increasing nearly that fast. In fact, it’s not increasing at all. On the contrary, since 2002 breast cancer incidence has actually declined, very likely due to the massive decrease in hormone replacement therapy use in the wake of the 2002 report from the Women’s Health Initiative showing that HRT doesn’t decrease cardiovascular risk but does increase the risk of breast cancer. Figure 1 in particular shows this trend, while Figure 2 shows what’s really driving the apparent increase in breast cancer diagnoses, a massive increase in the incidence of preinvasive DCIS.

We’ve known for quite some time that what’s driving this increase is nearly all mammographic screening; indeed, the article speculates that we may have finally reached the plateau in the increase of DCIS cases with the widespread use of mammographic screening over the last 20 years. That 12% figure is not just invasive cancer; it includes DCIS. While invasive cancer diagnoses are more or less stable, diagnoses of DCIS skyrocketed due to mammography. Indeed, this dovetails nicely with my earlier discussions of overdiagnosis due to mammography, because this is exactly what I’m talking about. Mammography picks up early cancers that may or may not ever threaten the life of the woman; that’s what overdiagnosis is. Moreover, overdiagnosis leads to overtreatment, as we don’t have a good handle on what percentage of DCIS lesions progress to life-threatening breast cancers if left alone. So we treat them all with surgery, nearly all of them with radiation, and most of them with Tamoxifen after surgery and radiation.

Unfortunately, in the article Kristof takes a somewhat reasonable suspicion and runs right off the dock with it into woo land, and Isis appears not to have been skeptical enough about his claims, given that she then used Kristof’s article as the basis for speculation that maybe African-American women, tending to be of lower socioeconomic status than Caucasian women, are exposed to more toxic chemicals and endocrine disruptors. Unfortunately, as Peter Lipson characterized his article, Kristof has clearly fallen for the “one true cause” fallacy so beloved of practitioners of woo, labeling endocrine disruptors such as BPA as a major environmental cause of the apparent increase in breast cancer diagnoses. Don’t get me wrong, there may well be something there in that BPA and endocrine disruptors may contribute to breast cancer, but almost certainly not to the extent that Kristof claims, even given the evidence he cites.

In addition, if there’s one thing about breast cancer, it’s that no single environmental exposure has been found to be strongly correlated with it; most of the correlations other than family history and exposure to hormone replacement therapy, including both positive and negative correlations, have been in general pretty weak. Indeed, I was recently peripherally involved in an effort to design a project to study environmental influences in breast cancer, and there are amazingly few validated environmental factors that increase the risk of breast cancer. Also, timing is very important; it may well be that it is exposure to these factors in adolescence or childhood in a “window” of susceptibility, not in adulthood, which is when they are normally studied. Right now, that’s where the current research efforts seem to be focused. In addition, breast density, which is primarily genetically determined, is a known risk factor for breast cancer as well, and investigators are actually planning to study that at our institution. All in all, it’s a hideously complicated business combining genetic and environmental factors that I am only beginning to wrap my brain around, while Kristof’s article was simplistic and alarmist in the extreme. For better information, I recommend a report from the Endocrine Society for the more sober, balanced perspective, and a report from the Breast Cancer Fund for arguments more explicitly in favor of a link. More information, including the chemical industry’s viewpoint (if you’re interested), can be found here.

I firmly believe that the recommendations for how we screen for breast cancer were overdue for an overhaul. Badly. However, the USPSTF guidelines may have gone too far too fast, at least for public consumption in light of the years of urging by the government and private advocacy organizations for all women over 40 to be screened, recommendations that say that mammography before age 50 may not be particularly beneficial were a hard pill to swallow. As I think about it more, though, one big flaw in the guidelines is that there was little consideration of how changing screening recommendations would impact special populations that may be at higher risk, such young African-American women. Worst of all, the USPSTF recommendations are an example of some of the astoundingly worst science communication I’ve seen in a long time. No groundwork was laid to prepare the public; the guidelines were just announced; and the spokespeople for the USPSTF looked like deer in the headlights when they showed up in the media to defend the guidelines. Specialty groups protecting their interests such as the American Radiologial Society and its President Dr. Kopans ate them for lunch and then laughed at their discomfiture. Meanwhile high ranking government officials couldn’t distance themselves fast enough, and lawmakers and ideologues had a field day playing politics with the guidelines.

In the end, while I still think that the new guidelines are reasonable for most non-black women, after thinking about it I doubt that they should be applied to African Americans. Finally, I’m now convinced more than ever that screening will only have limited effects in decreasing mortality from breast cancer, regardless of the test used, as long as we have so poor an understanding of the aspects of breast cancer biology that govern which early cancerous lesions will progress, which will not, and which will regress. Until we do, if there were developed a test to replace mammography, the same problems of overdiagnosis and overtreatment would remain. More than ever, we need to develop an understanding of the biology of breast cancer sufficiently advanced that it permits us to develop imaging tools and biological markers that can differentiate breast cancers that will progress and those that are not going to threaten the life of the woman. At the very least we need better indicators of risk. Until we have these things, screening will remain a highly imperfect tool that doesn’t save as many lives as it has the potential to.

ADDITIONAL READING ON MAMMOGRAPHY, BREAST CANCER, AND CANCER SCREENING:

1. The early detection of cancer and improved survival: More complicated than most people think
2. Early detection of cancer, part 2: Breast cancer and MRI
3. Do over one in five breast cancers detected by mammography alone really spontaneously regress?
4. PSA – To Screen or Not to Screen
5. Are one in three breast cancers really overdiagnosed and overtreated?
6. The cancer screening kerfuffle erupts again: “Rethinking” screening for breast and prostate cancer
7. The USPSTF recommendations for breast cancer screening: Not the final word
8. The Mammogram Post-Mortem