FROM THE EDITOR

Searching for lost car keys

There is an anecdote about a drunk, muttering to himself about losing his car keys after leaving a bar. A friend finds him on his hands and knees under the streetlight across the street from both the bar and his car, unable to find his keys (probably a good thing, given the circumstances). The friend points out the futility of looking for his lost keys across the street from his car, to which the drunk replies, “Yes, I know, but the light is much better over here!”

By coincidence, this issue of Menopausal Medicine addresses a topic that is presently a firestorm of controversy^1-3: breast cancer risk, detection, and screening. This past fall, Dr Laura Esserman, a renowned breast surgeon from San Francisco, published an insightful commentary on the state of breast cancer screening.⁴ In it, she and her coauthors provide insight into why mammography screening has not lived up to its expectations in terms of mortality prevention, and they make recommendations to tackle this problem at a fundamental level.

For those of us who practice obstetrics/gynecology, the story of the Pap smear has been a signature success of cancer prevention.⁵ Unlike breast cancer, cervical cancer follows a relatively indolent course in most cases. Unlike the breast epithelium, cervical epithelium is available for biopsy and direct visualization without a need for skin incision. To make matters even more favorable, precancerous lesions are readily amenable to complete excision. Arguably, the success story of the Pap smear has informed our approach to the prevention of breast cancer and has led us to a state of inappropriate optimism and faith in the screening test.

Unlike cervical cancer, there appears to be more variation in the rate of growth of breast tumors. Some tumors can go from undetectable to metastatic within a single screening interval.⁴ These more aggressive tumors tend to occur in younger women, and make annual mammographic screening in women in the age group of 40 to 50 considerably less cost-effective. This age group has always been a controversial one in terms of mammography screening guidelines, initiation of screening, and follow-up interval, with different experts making somewhat different recommendations over the years. In Esserman’s analysis, she discusses the fact that for both breast and prostate cancer, there has been less benefit than expected from mass screening paradigms. This is because low-grade lesions that will not cause death—and, in some cases, may even spontaneously regress⁶—are detected admirably well and excised, whereas the aggressive lesions, which are not “playing by the rules” we have learned with Pap smear screening, become metastatic in less than one screening interval and bedevil attempts at clinical detection. These more aggressive cancers are not decreasing at a rate that unequivocally justifies annual mammography for half of the population. The data lead us to the conclusion that the typical preventive cancer screening model that we embrace may be a flawed ideal. Thus, while we live in an era where improved breast cancer treatments have led to a 14% increase in 5-year survival (from 75% to 89% from 1975 to 2003⁷), are we really helping our patients by recommending annual screening beginning at age 40? Or are we simply generating more biopsies, sleepless nights, and overdiagnoses? Isn’t there a better way?

In November, the US Preventive Services Task Force (USPSTF) published its newest guidelines for breast cancer screening,⁸ an update of the 2002 guidelines⁹ (TABLE). These new guidelines were the equivalent of throwing gasoline onto a fire.

The biggest change is in the age at first screening, and herein lies the basis for the controversy. In order to save one woman in her 40s from death from breast cancer, 838 women would have to undergo annual screening for 6 years. This amount of screening would result in hundreds of biopsies and many low-aggression cancers being treated as if they were more aggressive than they really are.⁴ This represents a significant downside to the screening process and also makes it costly. However, it is not without benefit, as breast cancer strikes many women early in life and is the cancer that is associated with the most years of life lost. Many women, if faced with the risks of increased anxiety and possibly unnecessary biopsies and over-treatment, would be prepared to face these negative, costly disadvantages to avoid dying of breast cancer.

US Preventive Services Task Force guidelines for breast cancer screening

The way to improve the situation is not necessarily more mammography but, perhaps, better methods of risk evaluation. The USPSTF guidelines represent an accurate interpretation of the state of the art in mammographic detection of breast cancer. In the best of all possible worlds, doctors and their patients would be able to sort through personal preferences and background risk and come up with an acceptable screening plan for each patient under age 50. However, it is likely that third-party payers will interpret these guidelines as prohibitive of mammography prior to age 50, and many may choose not to pay for them. This will then leave the patient responsible for both the decision and the cost of the screening test. Sadly, then, the apparent “choice” in this situation will only accrue to women who can afford to pay out of pocket for their mammograms. Poor women will not have a choice.

Regardless of the social fallout and the media buzz generated by the new recommendations, we are still not where we want to be in terms of optimal breast cancer screening. By centering the controversy over the exact timing of mammography screening, we risk behaving like the drunk under the streetlight, looking for the key insight in the wrong place!

Breast cancer biology is a topic of intensive research, and there have been huge breakthroughs in recent years. Scientific insight into estrogen-receptor biology has led to major advances in estrogen-targeted prevention and chemotherapy.^10-12

In this issue of Menopausal Medicine, Drs Ghosh and Vachon provide a comprehensive examination of the importance of breast density as a dominant risk factor for the development of breast cancer, highlighting the role that genetics and hormones play in maintaining breast density in postmenopausal women. Increased breast density has emerged as a dominant, detectable, and modifiable risk factor for the subsequent development of breast cancer in women. In many ways, this issue’s authors provide a hopeful and constructive way to address the mammography controversy. It may be that future research can be directed toward the detection of preexisting conditions (such as gene mutations) that put women at risk for highly aggressive cancers. These women can be identified early in life. Additionally, factors that increase a more mature woman’s risk of cancer, such as breast density, can be identified in midlife. Enhanced imaging techniques, such as digital mammography and MRI,¹³ can be deployed effectively in this smaller group of high-risk women to arrive at a more balanced and appropriate ratio of not only cost-effectiveness but also harm to benefit.

It’s time to take out the flashlight, move away from the streetlight, and help the drunk make his way back to the car keys he dropped on his way out of the bar (and have a designated driver take him home, please!) We need to call upon medical science to come up with better ways to identify women at the highest risk for breast cancer and target intensive screening and prevention strategies to these women. We must not rely on mammography to “solve” the problem of early detection of breast cancer. We need to get back to the biology of this disease and outsmart it. We owe it to our patients.

Sexuality, Reproduction & Menopause ©2010 Lebhar-Friedman, Inc.