At a glance
- Numerous studies have affirmed that the usefulness of mammography increases with age.
- While not flawless, mammography currently represents our best method for breast-cancer screening.
- Data point heavily in favor or later initiation of Pap testing for women with normal Pap histories.
- Women at heightened risk of cervical cancer should continue to undergo annual Pap screening.
As clinicians, we are dually blessed and burdened with a plethora of evidence and opinions regarding the tests and treatments that we recommend to our patients. In no field has this been more true recently than in women’s health. Providers of preventive women’s health care face the challenge of sifting through newly released data and analysis and then reconciling that information with our own experiences and the needs of our patients.
Recently the U.S. Preventive Services Task Force (USPSTF) updated its recommendations for breast-cancer screening in the general population.1 To much conversation and uproar, the USPSTF advocate:
Continue Reading
- Shifting the starting age for mammography from age 40 years to age 50 years
- Scheduling mammograms biennially for women aged 50 to 74 years
- Possibly ceasing screening mammography at age 75 years
- Abandoning the routine teaching of breast self-examination to patients
Regarding clinical breast examination, the USPSTF found insufficient evidence to recommend for or against the practice in light of routine use of mammography.
In October 2011, the USPSTF proposed draft guidelines that would further the current trend toward less frequent, more targeted tests, suggesting that women younger than 65 years undergo Pap testing every three years, rather than annually as many clinicians continue to do, or even biannually, as current American College of Obstetrician and Gynecologist (ACOG) recommendations suggest.
Other proposed changes, suggest that screening be initiated at the age of 21 years in lieu of American College of Obstetrician and Gynecologist (ACOG) recommendations that state 21 years or within three years of initiating sexual activity as the criteria for Pap testing.
Currently, ACOG continues to call for Pap tests every two years for women aged 21 to 29 years, and every three years for women aged 30 to 65 years.
Both ACOG and USPSTF agree that women who have had previously normal Pap testing results and are not otherwise at risk should not continue to be tested after the age of 65 years. Cessation of Pap testing is also recommended after hysterectomy (with removal of the cervix) for benign disease. Women who have had abnormal Pap smears or who have other risk factors would have alternative schedules.
The public has endured a barrage of commentary on these topics during the past few years. Legislators, medical professionals, statisticians and health-care advocates have added their voices to the outcry. As clinicians, we have fielded countless questions from patients, colleagues, family and friends. Although most other professional societies have not adjusted their guidelines, all have issued responses, and speculation abounds that more change is ahead.
This article will explain the new recommendations and square them with current understandings of the state of the science, to help clinicians determine what is best for their patients.
Mammography
In 2009, 192,370 U.S. women were diagnosed with breast cancer, as were 1,910 men.3 A total of 40,170 women and 440 men died of the disease that year. The high incidence of breast cancer, combined with strong public messages surrounding the importance of early detection, has created a high demand for mammography and other screening technologies designed to detect disease at an early and treatable phase.
The medical community has struggled to educate women about cancer risk and ensure access to and funding for early detection. The news that mammography screening beginning at age 40 might not be best for all patients was therefore greeted with shock and skepticism by health-care professionals and the lay public alike.
The USPSTF characteristically ranks its recommendations according to the strength of the data analyzed. The task force gave biennial mammography for women aged 50 to 74 years a B grade, meaning that its members are moderately to highly certain of the technique’s routine benefit.
As for screening mammography before age 50 years, the USPSTF issued a C grade; this ranking indicates that the service should not be provided routinely but only when “other considerations” (e.g., elevated individual risk or strong patient preference) dictate.
The USPSTF also advised that there is insufficient evidence to recommend for or against routine screening mammography for women older than age 75 years. When insufficient evidence exists, the task force encourages that decisions be made on an individual basis and that patients be educated as to the benefits and harms of the procedure.
Although the USPSTF recommendations were widely regarded as surprising news, the understanding that the benefits of mammography vary by age is nothing new. Advancing age, after all, is the most significant determinant of a woman’s breast-cancer risk.
In 1997, biostatistician Virginia Ernster, PhD, chronicled the findings of the NIH consensus development conference on breast-cancer screening for women aged 40 to 49 years.4 NIH experts had determined that “data on the benefits and risks of screening mammography for women aged 40 through 49 are sufficiently mixed that informed decision making, rather than a blanket recommendation for all women, is an appropriate course of action.” This view, then as now, divided the medical community.
In the 13 years since that NIH conference, numerous studies have affirmed that the usefulness of mammography increases with age, especially from ages 50 to 65 years. The abundance of existing studies point to clear benefit for women aged 50 years and older but are ambivalent about screening in average-risk women between the ages of 40 and 50.5
Additionally, the cost-effectiveness of screening for women in their 40s is considerably lower than that for women aged 50 years and older.6 The strongest evidence of mammography’s benefit exists for women aged 60 to 69 years. No women older than age 75 years have participated in randomized clinical trials for breast-cancer screening.
In shaping its recommendations for women in their 40s, the USPSTF sought to incorporate data from studies conducted since the recommendations’ last iteration in 2002. Some of the data considered came from a 2006 study that quantified the reduction in 10-year mortality attributable to annual mammograms among women in their 40s.
The authors found that the benefit, while real, was not statistically significant.7 According to a recent systematic review cited by the USPSTF, one breast-cancer death could be prevented by screening 1,904 women aged 40 to 49 years; in contrast, only 1,339 women aged 50 to 59 years have to be screened to prevent one death.8 Modeling studies that appeared in the same issue of Annals of Internal Medicine as the updated USPSTF recommendations confirmed that in six of the eight most effective strategies analyzed, women began screening at age 50 years.9
Mammography currently represents our best method for breast-cancer screening but is by no means a flawless technology. With a high rate of false positives, mammograms can result in unnecessary biopsies and even in the treatment of insignificant growths that might have regressed otherwise. According to one study, a third of women screened with mammograms and clinical breast exams over a 10-year period would undergo follow-up for false-positive results.10
Nevertheless, most women surveyed for a 2004 study consider the risk of false-positive findings acceptable in order to detect early cancers.11 However, these false positives may result in disfiguring procedures, costly treatments with a range of side effects, and a high burden of anxiety.
According to a 2009 study, women with uncertain breast biopsy results had patterns of cortisol secretion comparable to those of women with a diagnosis of cancer.12 Elevated cortisol, indicative of emotional and/or physical stress, can contribute to chronic and episodic illness.
Much of the confusion regarding the utility of early and frequent breast-cancer screening can be attributed to the ongoing controversy surrounding ductal carcinoma in situ (DCIS). DCIS is a common, noninvasive breast condition that can progress to invasive breast cancer when left untreated.
It is generally diagnosed by mammography and treated with surgery and/or radiation, often followed by hormone therapy. Many cases of DCIS will not develop into cancer or will grow extremely slowly, leading some experts to worry that DCIS may currently be overdiagnosed or overtreated, particularly in younger women.
While many argue that false-positive tests and their subsequent follow-up are a small price to pay for the security of thorough screening, mammography can have disappointingly limited sensitivity, especially in younger women with dense breasts. Estimates of the test’s sensitivity generally fall near the 75% mark. According to data from the National Cancer Institute, younger women — especially those with dense breasts or fast-growing tumors—are more likely than older women to be diagnosed with breast cancer following a negative mammogram.13
Studies also show that women younger than age 50 benefit from screening by digital rather than film mammography, but the USPSTF regards the present evidence as insufficient for a large-scale recommendation favoring digital mammography.14
Importantly, screening recommendations apply only to average-risk patients. Women with a family history of breast cancer or other risk factors should have a personalized schedule. High-risk women also may be candidates for MRI; the sensitivity of MRI has been reported to be as high as 100% in some studies. However, the procedure is costly.15
The American Cancer Society calls for MRI as an adjunct to mammography for women with mutations in the BRCA gene and for those with a history of chest radiation (usually for Hodgkin’s disease), as well as a limited number of others.16 If a woman has a first-degree relative with a history of breast cancer, her own lifetime risk of breast cancer doubles; such women are generally counseled to begin screening when they are five to 10 years younger than the age at which their relative was diagnosed. Women with a known genetic risk frequently begin screening between the ages of 25 and 35 years.17 Having a male family member with breast cancer also is a strong risk factor; genetic counseling may be indicated for these patients.
In addition to family history, genetic mutations and history of chest radiation, other components of a woman’s medical history are germane to determining her risk of breast cancer. Table 1 lists more factors related to a woman’s medical history that should be considered in determining her breast-cancer risk.
For women with an elevated chance of contracting breast cancer, the mammography calculus might be more weighted toward earlier screening. Patients should also be carefully counseled about techniques to address modifiable risk factors (i.e., reducing alcohol consumption and maintaining a normal weight).
When placed in context with existing knowledge about breast cancer and mammography, the seemingly radical USPSTF recommendations simply amount to one more step in the ongoing questioning of the reliability of screening mammograms.
Because we currently lack a more sensitive or specific modality for screening in the general population, ACOG, the American Cancer Society, and the American College of Radiology have declined to change their guidelines and still recommend that women begin receiving mammograms at age 40 years. Many health-care providers and experts have spoken out against the new USPSTF document, concerned cancers that might have been detected early will be missed.
Ultimately, the mammography debate can be boiled down to differing valuations of individual and public health and differing calculations of the risks and benefits of testing. Few would dispute the fact that screening women from age 40 years on will catch some cancers earlier. But those who advocate starting screening at a later age emphasize the financial, emotional and physical costs of those hundreds of thousands of tests each year.
While the USPSTF recommendations do represent an evidence-based approach to care, its standards are not yet accepted practice, and most clinicians are apt to delay implementing changes until other professional societies have endorsed such adjustments. Understanding the underlying data will enable us to understand the present debate and advise our patients appropriately.
Although it did not ignite as much controversy as the change in mammogram guidelines, the USPSTF’s questioning of breast self-examination (BSE) also deserves attention. In 2002, a now famous trial by Thomas et al found that BSE instruction did not reduce breast-cancer mortality but did increase the likelihood of a benign breast biopsy.18
One of the limitations of BSE, according to this study and others, is the detection of a transient, nonmalignant mass, which often leads to unnecessary testing, cost and stress. Also, women are likely to check their own breasts incidentally even without specific instructions from a health-care provider. As many argue, BSE may facilitate the detection of a mass, but it is not shown to decrease breast-cancer mortality.
A smaller study focused on a patient population at high risk for breast cancer (approximately 20% average lifetime risk). The researchers found that BSE was effective in detecting cancer between screening tests.19 Based on the divergences between their findings and those of the 2002 study by Thomas and colleagues, the authors proposed that three factors may be crucial to the evaluation of BSE: “(1) the motivation of women to perform BSE, (2) combined CBE [clinical breast examination]/BSE teaching by a highly trained provider, and (3) the ability of women to directly report BSE findings to a provider and receive rapid clinical follow-up.”
Therefore, it was argued, BSE should not be abandoned, particularly by high-risk women. BSE, like CBE, is especially valuable to people in medically underserved areas in which access to mammography is scarce, and to high-risk individuals.
So, what do you tell your patients? As the USPSTF advises, individual patients’ medical and psychological needs should be considered when prescribing screening tests. Women who are adamant about starting mammograms at age 40 can certainly still do so, as long as they understand the true benefits and limitations of the test.
If your patient is at high risk of breast cancer for lifestyle reasons or because of family history, early screening is advisable. And of course any patient with a palpable lump on SBE or CBE needs immediate follow-up with mammogram and/or ultrasound. For patients at average risk, however, delaying the start of screening mammography until age 50 may be considered prudent and justifiable if doing so is in accordance with the woman’s health profile and values.
Pap testing
While confusion surrounds breast-cancer screening, existing data point heavily in favor of later initiation of Pap testing and expanded inter-test intervals for women with normal Pap histories.
The remarkable 50% reduction in cervical cancer rates over the past 30 years, combined with emerging understanding of the virology and epidemiology of human papillomavirus (HPV), has facilitated an increasingly informed, evidence-based approach to cervical cancer screening.
The annual Pap smear was once considered a critical component of women’s health care, but the past decade has seen a relaxation of that standard, as well as the introduction of other tests to predict a woman’s cancer risk.
HPV testing is now routinely employed to determine plans for women with atypical squamous cells of undetermined significance Pap results. It is used along with cytology to determine appropriate Pap screening schedules for women aged 30 years and older.
Citing a low rate of cervical cancer among younger women, ACOG now recommends that women begin Pap screening at age 21 years. Previous guidelines called for the first Pap test to be done three years after the onset of sexual activity or at age 21 years, whichever occurred sooner.
Although many sexually active young women show evidence of HPV infection, most will clear the virus to undetectable levels within one to two years. Studies show that fewer than 6% of women aged 12 to 18 years have Pap results showing low-grade squamous intraepithelial lesions (LSILs), and fewer than 1% have high-grade squamous intraepithelial lesions.20 Of those with LSIL, 91% regress to normal within three years.
Those findings had already persuaded ACOG and the American Society for Colposcopy and Cervical Pathology to recommend a conservative approach to the management of cervical dysplasia in adolescents, generally calling for repeat Pap tests rather than immediate intervention.
As ACOG’s practice bulletin states, “Delaying the onset of screening until age 21 years is a logical incremental step in practice guidelines, consistent with this conservative approach to management of adolescents with cervical test result abnormalities.”2
The main motivation for delaying screening of adolescents is to avoid unnecessary treatment. Excisional procedures for the treatment of cervical dysplasia can predispose women to preterm labor later in life, raising the risk of low birth weight, developmental problems, and respiratory difficulty in the neonate.
For women aged 21 to 29 years, ACOG now recommends a Pap test every two years rather than annually. At age 30, HPV DNA testing and cytology are recommended. If both tests are negative, the screening interval can be widened to every three years. (With positive HPV DNA, even in the presence of negative cytology, colposcopy is indicated. Abnormal cytology is managed according to normal protocols.) Per the new guidelines, 30-year-old women who have had three consecutive normal Pap tests, even in the absence of HPV testing, can extend the Pap interval to three years.
In a more recent development, USPSTF released draft recommendations this week proposing to change it’s guidelines to recommend three year intervals for all women aged younger than 65. The draft is open to public comment until Nov. 16, 2011.
Women at heightened risk of cervical cancer should continue to undergo annual screening. This includes women with HIV, who should have Pap testing every six months during the first year after diagnosis, followed by annual screening; immune-suppressed women, including those taking medications after transplant surgery; women exposed to DES in utero; and women with a history of cervical intraepithelial neoplasia (CIN)-2, CIN-3 or cervical cancer.
Because most women are exposed to HPV shortly after the onset of sexual activity, the presence of the virus in older women generally represents persistent rather than new infection. ACOG recommends that women cease regular Pap screening once they reach 65 to 70 years of age.
However, older women with multiple sexual partners, while at lower risk for CIN than younger women, should still be screened routinely. Also, women with a history of abnormal cytology should not discontinue screening entirely until 10 years after the last abnormal result, but the interval between tests can be widened to every three years after three consecutive normal tests. Women with a history of CIN-2 or higher remain at risk of recurrence for 20 years following treatment, during which time they should undergo annual screening.
Despite ACOG’s dismissal of the annual Pap smear as “tradition,” the convention of an annual well-woman visit remains important for many women. This is especially true for the as many as one-third of women who seek primary care in a women’s health setting.21
The annual exam serves as an opportunity to screen women for sexually transmitted infections22 and other gynecologic conditions and address family planning and such preventive health topics as smoking, substance use, exercise and nutrition. Screening for physical and mental health problems is also an important component of the annual visit, as is assessing a woman’s safety at home and in the workplace.
Conclusion
As we navigate the data regarding women’s health screening tests, we must continually remember to take the complete patient into account. Many women perceive breast cancer to be their primary health risk and may accordingly miscalculate their risk for such conditions as heart disease and lung cancer, which are, respectively, more common and more deadly.23
As we rethink guidelines for cancer screening, we must also be diligent in reminding women about other preventive health themes that might not be splashed daily across their newspapers — smoking cessation, mainting healthy weight, stress reduction and regular exercise.
In addition to lowering risks of some reproductive cancers, these behaviors will reduce a woman’s risk for chronic illnesses. Colonoscopy, fecal occult blood testing, cholesterol testing, blood glucose testing and other patient-specific screening tests should not fall by the wayside as we deal with breast and cervical cancer guidelines.
Health-care access should also remain a primary concern. Half the women diagnosed each year with cervical cancer had never had prior screening. In addition to advising our current patients about their health risks and conducting appropriate testing, we must remain mindful of those who lack care and facilitate their access to timely preventive services. Our patients and the public look to us to safeguard their overall health and to maintain perspective amid a flurry of evidence and opinions.
Lisa Stern, MSN, APRN, is the Research Manager of Planned Parenthood Federation of America.
References
1. U.S. Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;151:716-727.
2. American College of Obstetricians and Gynecologists Committee on Practice Bulletins—Gynecology. Cervical cytology screening. ACOG Practice Bulletin Number 109. Obstet Gynecol. 2009;114:1409-1420.
3. U.S. National Institutes of Health. National Cancer Institute Web site: breast cancer.
4. Ernster VE. Mammography screening for women aged 40 through 49—a guidelines saga and a clarion call for informed decision making. Am J Public Health. 1997;87:1103-1106.
5. Moss S. Should women under 50 be screened for breast cancer? Br J Cancer. 2004;91:413-417.
6. Salzmann P, Kerlikowske K, Phillips K. Cost-effectiveness of extending screening mammography guidelines to include women 40 to 49 years of age. Ann Intern Med. 1997;127:955-965.
7. Moss SM, Cuckle H, Evans A, et al. Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years’ follow-up: a randomised controlled trial. Lancet. 2006;368:2053-2060.
8. Nelson HD, Tyne K, Naik A, et al. Screening for breast cancer: an update for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;151:727-737.
9. Mandelblatt JS, Cronin KA, Bailey S, et al. Effects of mammography screening under different screening schedules: model estimates of potential benefits and harms. Ann Intern Med. 2009;151:738-747.
10. Elmore JG, Barton MB, Moceri VM, et al. Ten-year risk of false positive screening mammograms and clinical breast examinations. N Engl J Med. 1998:338:1089-1096.
11. Schwartz LM, Woloshin S, Fowler FJ, Welch HG. Enthusiasm for cancer screening in the United States. JAMA. 2004;291:71-78.
12. Lang EV, Berbaum KS, Lutgendorf SK. Large-core breast biopsy: abnormal salivary cortisol profiles associated with uncertainty of diagnosis. Radiology. 2009;250:631-637.
13. Buist DSM, Porter PL, Lehman C, et al.: Factors contributing to mammography failure in women aged 40-49 years. J Natl Cancer Inst. 2004;96:1432-1440.
14. Pisano ED, Gatsonis C, Hendrick E, et al. Diagnostic performance of digital versus film mammography for breast-cancer screening. N Engl J Med. 2005;353:1773-1783.
15. Kriege M, Brekelmans CTM, Boetes C, et al. Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med. 2004;351:427-437.
16. Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75-89.
17. Narod SA, Offit K. Prevention and management of hereditary breast cancer. J Clin Oncol. 2005;23:1656-1663.
18. Thomas DB, Gao DL, Ray RM, et al. Randomized trial of breast self-examination in Shanghai: final results. J Natl Cancer Inst. 2002;94:1445-1457.
19. Wilke LG, Broadwater G, Rabiner S, et al. Breast self-examination: defining a cohort still in need. Am J Surg. 2009;198:575-579.
20. Wright JD, Davila RM, Pinto KR, et al. Cervical dysplasia in adolescents. Obstet Gynecol. 2005;106:115-120.
21. Scholle SH, Kelleher K. Assessing primary care performance in an obstetrics/gynecology clinic. Women Health. 2003;37:15-30.
22. U.S. Department of Health & Human Services. New Pap test guidelines: start later, have fewer. The National Women’s Health Information Center Web site. November 20, 2009.
23. Brody JE. Communicating cancer risk in print journalism. J Natl Cancer Inst Monogr. 1999;25:170-172.
This document was last updated Oct. 25, 2011.
