What price reassurance?

Dr. Lockwood, Editor-in-Chief, is Dean of the Morsani College of Medicine and Senior Vice President of USF Health, University of South Florida, Tampa. Send your feedback to: DrLockwood@advanstar.com

The incidence of breast cancer has been declining for more than a decade, perhaps as a result of the dramatic reduction in the use of postmenopausal therapy with combined estrogen and progestin. Far more significantly, breast cancer deaths have been declining for the past 25 years.¹ This is likely due to an improved understanding of relevant cancer biology, better therapies, and advances in screening technologies and their utilization. However, the prevalence of breast cancer rises with age, making screening more efficacious in older women and lowering the positive predictive value (PPV) of screening in younger women. For example, routine mammograms have a PPV of 1.6% among women aged 40 to 44 versus 5.9% for women aged 60 to 64 years.² Conversely, the higher rate of extremely dense breasts in younger women leads to lower mammographic screening sensitivity (73.4% for women aged 40 to 44 vs 84.7% for those aged 60 to 64 years).² Thus, 1904 women in their 40s would need to be screened to prevent one breast cancer death, while only 377 women in their 60s would need to be screened to avoid one such death.³

Also read: Salpingo-oophorectomy: benefits confirmed for some gynecologic breast cancers

Thus, while meta-analyses suggest that mammography reduces the relatively uncommon (< 1 per 1000) occurrence of breast cancer death among women aged 39 to 49 by around 15% (relative risk, 0.85 [95% credible interval, 0.75–0.96]; 8 trials),³ such screening is associated with substantially increased costs due to both false-positive results and overdiagnosis of lesions that would not necessarily lead to mortality. But just how much expense does such screening add to the health system? A recent study suggests far more than previously thought.

The cost of false-positives and overdiagnosis

Ong and Mandl conducted a retrospective cohort study of 702,154 women aged 40 to 59 years who underwent routine mammography during a 12-month period. The researchers used insurance data to calculate the expense of false-positive mammograms and breast cancer overdiagnoses.⁴ They included beneficiaries from all 50 states and the District of Columbia undergoing such screening in 2012 who were continuously enrolled in the insurance plan for the following 12 months. They excluded high-risk women, including those with a prior diagnosis of breast cancer.

The authors defined a “false-positive mammogram” as one that led to a further diagnostic workup that was not followed by a breast cancer diagnosis. Women with invasive breast cancers were identified by the ICD-9 code for invasive breast cancer (174.x) as well as by evidence of subsequent breast cancer treatment (ie, surgery, radiation therapy, or chemotherapy). Women with ductal carcinoma in situ (DCIS) were also defined by ICD-9 code (233.0). Since the authors could not ascertain from insurance claims which breast cancers had been overdiagnosed, they used published rates to estimate this occurrence. They then estimated annual national costs by applying the false-positive rate derived from their analysis and overdiagnosis rates reported in the recent literature to their average cost data, extrapolating these costs to the number of women screened annually in the United States.

Related: More money spent on breast Ca screening may not lead to better outcomes 

The authors reported that 77,729 women (11.1%) had a false-positive mammogram result requiring a further diagnostic workup and breast-related procedures. Defining breast ultrasound and magnetic resonance imaging as part of that work-up increased the number of false-positive mammogram results to 91,501 (13%). As expected, women aged 40 to 49 years were more likely to have a false-positive result than were those aged 50 to 59 years (14.4% vs 11.6%, odds ratio 1.25; 95%CI: 1.23–1.26). Among those with a false-positive mammogram, a biopsy was performed in 29.3% of cases and 0.4% of patients underwent a prophylactic mastectomy.

The average cost per beneficiary for a false-positive result was $852, with $200 in out-of-pocket expenses. Given that there are about 21.2 million women aged 40–49 and 22.4 million aged 50–59 in the United States, and assuming 62.3% and 72.6% of these 2 cohorts, respectively, undergo mammography screening each year, 29.5 million women would be screened. Given an 11% false-positive rate, 3.2 million would undergo unnecessary studies for a total cost of $2.8 billion per year. Using these data, women aged 40 to 49 years would generate $1.24 billion per year in excess costs from false-positive mammograms.

The occurrence of invasive breast cancer within 12 months of a mammogram was found to be 0.3% for women aged 40 to 49 and 0.4% for those aged 50 to 59 years, while ductal carcinoma in situ (DCIS) was detected relatively rarely in both groups (<0.1%). The average cost of care for each patient with invasive breast cancer was $51,837 with $3,019 in out-of-pocket expenses. Costs were greater for those aged 40 to 49 versus than for those aged 50 to 59 years ($53,894 vs $50,299), in part because younger women were more likely to undergo total mastectomies (41% vs 30.4%) and breast reconstruction (35.6% vs 25.4%).

Based on recent literature, the authors estimated that 22% of all screen-detected invasive breast cancers were overdiagnoses and concluded that in the United States in 2012, 20,116 women aged 40 to 59 were overdiagnosed with invasive breast cancer, generating another $1 billion in unnecessary cost. For DCIS, overdiagnosis would have cost an additional $243 million. Because roughly half of these 2 combined costs can be ascribed to women aged 40 to 49, routine screening mammography in this younger group generates about $2 billion in excess costs. And that figure does not include the cost of the excess anxiety generated by false-positive results.⁵

Take-home message

In light of the reduced diagnostic efficacy of routine mammography in younger women, the lower prevalence of the disease in this group, and concerns about costs, the US Preventive Services Task Force (USPSTF) in 2009 recommended against routine mammography screening for women aged 40 to 49.⁶ They also recommended biennial (every 2-year) screening thereafter.

The latest USPSTF draft recommendations, released on April 20, 2015, also do not endorse routine screening for women aged 40 to 49 but recommend informed, individualized decision-making based on a woman's “values, preferences, and health history.”⁷ A press release accompanying the draft recommendations explained: “For women in their 40s, the Task Force found that mammography screening every two years can also be effective and recommends that the decision to start screening should be an individual one, recognizing the potential benefits as well as the potential harms. The Task Force opined that some women in their 40s will benefit from mammography, most will not, while others will be harmed. Of the potential harms, the most serious is unneeded diagnosis and treatment for a type of breast cancer that would not have become a threat to a woman's health during her lifetime. The most common harm is a false-positive test result, which often leads to additional tests and procedures.  They also noted that, “Among women in their 40s, women who have a mother, sister, or daughter with breast cancer may benefit more than average-risk women by beginning screening before age 50. The Task Force rated this recommendation as a C, noting that mammography for women in their 40s is effective in reducing deaths from breast cancer, but that the benefits are less than for older women and the harms potentially greater.” 

In contrast, the American College of Obstetricians and Gynecologists (ACOG), the American Medical Association, and the American Cancer Society recommend starting screening at age 40 and conducting it annually, with varying age recommendations as to when to stop. Unfortunately, while the US government doesn’t need to worry about the plaintiff’s bar, ob/gyns do, so I doubt many of my colleagues plan to deviate from the ACOG guidelines based on Ong and Mandl’s study.

However, it is clearly time to develop a more rational and cost-effective approach to breast cancer screening, one that combines demographic, family history, and clinical parameters such as those found in the Gail Model (a version is found at the National Cancer Institute website at www.cancer.gov/bcrisktool/) with genomic and perhaps biochemical tests. I predict that breast cancer screening will follow the evolution seen in obstetrics with aneuploidy screening, wherein maternal age as the sole criteria for testing was replaced by multiple parameters (eg, biochemical, sonographic, and now cell-free fetal DNA testing). But even in such a setting, for an individual woman, the desire to be reassured by screening should be respected. The question is: Who pays the price for such reassurance?

References

1. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61(4):212–236.

2. National Cancer Institute. Performance measures for 1,838,372 screening mammography examinations from 2004 to 2008 by age: based on BCSC data through 2009. http://breastscreening.cancer.gov/statistics/performance/screening/2009/perf_age.html. Accessed April 19, 2015.

3. Nelson HD, Tyne K, Naik A, Bougatsos C, Chan BK, Humphrey L; U.S. Preventive Services Task Force. Screening for breast cancer: an update for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;151(10):727–737, W237–42.

4. Ong MS, Mandl KD. National expenditure for false-positive mammograms and breast cancer overdiagnoses estimated at $4 billion a year. Health Aff. (Millwood). 2015;34(4):576–583.

5. Tosteson AN, Fryback DG, Hammond CS, et al. Consequences of false-positive screening mammograms. JAMA Intern Med. 2014;174(6):954–961.

6. US Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;151(10):716–726.

7. US Preventive Services Task Force. Draft Recommendation Statement: Breast Cancer: Screening. http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementDraft/breast-cancer-screening1. Accessed April 21, 2015.