Article Type
Article
Changed
Tue, 02/28/2023 - 12:05
Author(s)
Mark D. Pearlman, MD

 

Meaningful progress has been made in reducing deaths due to breast cancer over the last half century, with a 43% decrease in mortality rate (breast cancer deaths per 100,000 population).1 Screening mammography (SM) has contributed greatly to that success, accounting for 30% to 70% of the reduced mortality rate, with the remainder due to advancements in breast cancer treatment.2 Despite these improvements, invasive breast cancer remains the highest incident cancer in the United States and in the world, is the second leading cause of cancer death in the United States, and results in more years of life lost than any other cancer (TABLE 1).1,3

While the benefits and harms of SM are reasonably well understood, different guidelines groups have approached the relative value of the risks and benefits differently, which has led to challenges in implementation of shared decision making, particularly around the age to initiate routine screening.4-6 In this article, we will focus on the data behind the controversy, current gaps in knowledge, challenges related to breast density and screening in diverse groups, and emerging technologies to address these gaps and provide a construct for appropriate counseling of the patient across the risk spectrum.

New series on cancer screening

In recognition of 35 years of publication of OBG Management, this article on breast cancer screening by Mark D. Pearlman, MD, kicks off a series that focuses on various cancer screening modalities and expert recommendations.

Stay tuned for articles on the future of cervical cancer screening and genetic testing for cancer risk beyond BRCA testing.

We look forward to continuing OBG Management’s mission of enhancing the quality of reproductive health care and the professional development of ObGyns and all women’s health care clinicians.

 

Breast cancer risk

Variables that affect risk

While female sex and older age are the 2 greatest risks for the development of breast cancer, many other factors can either increase or decrease breast cancer risk in a person’s lifetime. The importance of identifying risk factors is 3-fold:

  1. to perform risk assessment to determine if individuals would benefit from average-risk versus high-risk breast cancer surveillance
  2. to identify persons who might benefit from BRCA genetic counseling and screening, risk reduction medications or procedures, and
  3. to allow patients to determine whether any modification in their lifestyle or reproductive choices would make sense to them to reduce their future breast cancer risk.

Most of these risk variables are largely inalterable (for example, family history of breast cancer, carriage of genetic pathogenic variants such as BRCA1 and BRCA2, age of menarche and menopause), but some are potentially modifiable, such as parity, age at first birth, lactation and duration, and dietary factors, among others. TABLE 2 lists common breast cancer risk factors.

Breast cancer risk assessment

Several validated tools have been developed to estimate a person’s breast cancer risk (TABLE 3). These tools combine known risk factors and, depending on the specific tool, can provide estimates of 5-year, 10-year, or lifetime risk of breast cancer. Patients at highest risk can benefit from earlier screening, supplemental screening with breast magnetic resonance imaging (MRI), or risk reduction (see the section, “High-risk screening”). Ideally, a risk assessment should be done by age 30 so that patients at high risk can be identified for earlier or more intensive screening and for possible genetic testing in those at risk for carriage of the BRCA or other breast cancer gene pathogenic variants.5,7

Continue to: Breast cancer screening: Efficacy and harms...

 

 

Breast cancer screening: Efficacy and harms

The earliest studies of breast cancer screening with mammography were randomized controlled trials (RCTs) that compared screened and unscreened patients aged 40 to 74. Nearly all the RCTs and numerous well-designed incidence-based and case-control studies have demonstrated that SM results in a clinically and statistically significant reduction in breast cancer mortality (TABLE 4).4,6,8 Since the mid-1980s and continuing to the current day, SM programs are routinely recommended in the United States. In addition to the mortality benefit outlined in TABLE 4, SM also is associated with a need for less invasive treatments if breast cancer is diagnosed.9,10

With several decades of experience, SM programs have demonstrated that multiple harms are associated with SM, including callbacks, false-positive mammograms that result in a benign biopsy, and overdiagnosis of breast cancer (TABLE 4). Overdiagnosis is a mammographic detection of a breast cancer that would not have harmed that woman in her lifetime. Overdiagnosis leads to overtreatment of breast cancers with its attendant side effects, the emotional harms of a breast cancer diagnosis, and the substantial financial cost of cancer treatment. Estimates of overdiagnosis range from 0% to 50%, with the most likely estimate of invasive breast cancer overdiagnosis from SM between 5% and 15%.11-13 Some of these overdiagnosed cancers are due to very slow growing cancers or breast cancers that may even regress. However, the higher rates of overdiagnosis occur in older persons who are screened and in whom competing causes of mortality become more prevalent. It is estimated that overdiagnosis of invasive breast cancer in patients younger than age 60 is less than 1%, but it exceeds 14% in those older than age 80 (TABLE 4).14

A structured approach is needed to counsel patients about SM so that they understand both the substantial benefit (earlier-stage diagnosis, reduced need for treatment, reduced breast cancer and all-cause mortality) and the potential harms (callback, false-positive results, and overdiagnosis). Moreover, the relative balance of the benefits and harms are influenced throughout their lifetime by both aging and changes in their personal and family medical history.

 


Counseling should consider factors beyond just the performance of mammography (sensitivity and specificity), such as the patient’s current health and age (competing causes of mortality), likelihood of developing breast cancer based on risk assessment (more benefit in higher-risk persons), and the individual patient’s values on the importance of the benefits and harms. The differing emphases on mammography performance and the relative value of the benefits and harms have led experts to produce disparate national guideline recommendations (TABLE 5).

Should SM start at age 40, 45, or 50 in average-risk persons?

There is not clear consensus about the age at which to begin to recommend routine SM in patients at average risk. The National Comprehensive Cancer Network (NCCN),7 American Cancer Society (ACS),4 and the US Preventive Services Task Force (USPSTF)5 recommend that those at average risk start SM at age 40, 45, and 50, respectively (TABLE 5). While the guideline groups listed in TABLE 5 agree that there is level 1 evidence that SM reduces breast cancer mortality in the general population for persons starting at age 40, because the incidence of breast cancer is lower in younger persons (TABLE 6),4 the net population-based screening benefit is lower in this group, and the number needed to invite to screening to save a single life due to breast cancer varies.

For patients in their 40s, it is estimated that 1,904 individuals need to be invited to SM to save 1 life, whereas for patients in their 50s, it is 1,339.15 However, for patients in their 40s, the number needed to screen to save 1 life due to breast cancer decreases from 1 in 1,904 if invited to be screened to 1 in 588 if they are actually screened.16 Furthermore, if a patient is diagnosed with breast cancer at age 40–50, the likelihood of dying is reduced at least 22% and perhaps as high as 48% if her cancer was diagnosed on SM compared with an unscreened individual with a symptomatic presentation (for example, palpable mass).4,15,17,18 Another benefit of SM in the fifth decade of life (40s) is the decreased need for more extensive treatment, including a higher risk of need for chemotherapy (odds ratio [OR], 2.81; 95% confidence interval [CI], 1.16–6.84); need for mastectomy (OR, 3.41; 95% CI, 1.36–8.52); and need for axillary lymph node dissection (OR, 5.76; 95% CI, 2.40–13.82) in unscreened (compared with screened) patients diagnosed with breast cancer.10

The harms associated with SM are not inconsequential and include callbacks (approximately 1 in 10), false-positive biopsy (approximately 1 in 100), and overdiagnosis (likely <1% of all breast cancers in persons younger than age 50). Because most patients in their 40s will not develop breast cancer (TABLE 6), the benefit of reduced breast cancer mortality will not be experienced by most in this decade of life, but they are still just as likely to experience a callback, false-positive biopsy, or the possibility of overdiagnosis. Interpretation of this balance on a population level is the crux of the various guideline groups’ development of differing recommendations as to when screening should start. Despite this seeming disagreement, all the guideline groups listed in TABLE 5 concur that persons at average risk for breast cancer should be offered SM if they desire starting at age 40 after a shared decision-making conversation that incorporates the patient’s view on the relative value of the benefits and risks.

Continue to: High-risk screening...

 

 

High-risk screening

Unlike in screening average-risk patients, there is less disagreement about screening in high-risk groups. TABLE 7 outlines the various categories and recommended strategies that qualify for screening at younger ages or more intensive screening. Adding breast MRI to SM in high-risk individuals results in both higher cancer detection rates and less interval breast cancers (cancers diagnosed between screening rounds) diagnosed compared with SM alone.19,20 Interval breast cancer tends to be more aggressive and is used as a surrogate marker for more recognized factors, such as breast cancer mortality. In addition to less interval breast cancers, high-risk patients are more likely to be diagnosed with node-negative disease if screening breast MRI is added to SM.

Long-term mortality benefit studies using MRI have not been conducted due to the prolonged follow-up times needed. Expense, lower specificity compared with mammography (that is, more false-positive results), and need for the use of gadolinium limit more widespread use of breast MRI screening in average-risk persons.

 

Screening in patients with dense breasts

Half of patients undergoing SM in the United States have dense breasts (heterogeneously dense breasts, 40%; extremely dense breasts, 10%). Importantly, increasing breast density is associated with a lower cancer detection rate with SM and is an independent risk factor for developing breast cancer. While most states already require patients to be notified if they have dense breasts identified on SM, the US Food and Drug Administration will soon make breast density patient notification a national standard (see: https://delauro.house.gov/media-center/press-releases/delauro-secures-timeline-fda-rollout-breast-density-notification-rule).

Most of the risk assessment tools listed in TABLE 3 incorporate breast density into their calculation of breast cancer risk. If that calculation places a patient into one of the highest-risk groups (based on additional factors like strong family history of breast cancer, reproductive risk factors, BRCA carriage, and so on), more intensive surveillance should be recommended (TABLE 7).7 However, once these risk calculations are done, most persons with dense breasts will remain in an average-risk category.

Because of the frequency and risks associated with dense breasts, different and alternative strategies have been recommended for screening persons who are at average risk with dense breasts. Supplemental screening with MRI, ultrasonography, contrast-enhanced mammography, and molecular breast imaging are all being considered but have not been studied sufficiently to demonstrate mortality benefit or cost-effectiveness.

Of all the supplemental modalities used to screen patients with dense breasts, MRI has been the best studied. A large RCT in the Netherlands evaluated supplemental MRI screening in persons with extremely dense breasts after a negative mammogram.21 Compared with no supplemental screening, the MRI group had 17 additional cancers detected per 1,000 screened and a 50% reduction in interval breast cancers; in addition, MRI was associated with a positive predictive value of 26% for biopsies. At present, high cost and limited access to standard breast MRI has not allowed its routine use for persons with dense breasts in the United States, but this may change with more experience and more widespread introduction and experience with abbreviated (or rapid) breast MRI in the future (TABLE 8).

Equitable screening

Black persons who are diagnosed with breast cancer have a 40% higher risk of dying than White patients due to multiple factors, including systemic racial factors (implicit and unconscious bias), reduced access to care, and a lower likelihood of receiving standard of care once diagnosed.22-24 In addition, Black patients have twice the likelihood of being diagnosed with triple-negative breast cancers, a biologically more aggressive tumor.22-24 Among Black, Asian, and Hispanic persons diagnosed with breast cancer, one-third are diagnosed younger than age 50, which is higher than for non-Hispanic White persons. Prior to the age of 50, Black, Asian, and Hispanic patients also have a 72% more likelihood of being diagnosed with invasive breast cancer, have a 58% greater risk of advanced-stage disease, and have a 127% higher risk of dying from breast cancer compared with White patients.25,26 Based on all of these factors, delaying SM until age 50 may adversely affect the Black, Asian, and Hispanic populations.

Persons in the LGBTQ+ community do not present for SM as frequently as the general population, often because they feel threatened or unwelcome.27 Clinicians and breast imaging units should review their inclusivity policies and training to provide a welcoming and respectful environment to all persons in an effort to reduce these barriers. While data are limited and largely depend on expert opinion, current recommendations for screening in the transgender patient depend on sex assigned at birth, the type and duration of hormone use, and surgical history. In patients assigned female sex at birth, average-risk and high-risk screening recommendations are similar to those for the general population unless bilateral mastectomy has been performed.28 In transfeminine patients who have used hormones for longer than 5 years, some groups recommend annual screening starting at age 40, although well-designed studies are lacking.29

Continue to: We have done well, can we do better?...

 

 

We have done well, can we do better?

Screening mammography clearly has been an important and effective tool in the effort to reduce breast cancer mortality, but there are clear limitations. These include moderate sensitivity of mammography, particularly in patients with dense breasts, and a specificity that results in either callbacks (10%), breast biopsies for benign disease (1%), or the reality of overdiagnosis, which becomes increasingly important in older patients.

With the introduction of mammography in the mid-1980s, a one-size-fits-all approach has proved challenging more recently due to an increased recognition of the harms of screening. As a result of this evolving understanding, different recommendations for average-risk screening have emerged. With the advent of breast MRI, risk-based screening is an important but underutilized tool to identify highest-risk individuals, which is associated with improved cancer detection rates, reduced node-positive disease, and fewer diagnosed interval breast cancers. Assuring that nearly all of this highest-risk group is identified through routine breast cancer risk assessment remains a challenge for clinicians.

But what SM recommendations should be offered to persons who fall into an intermediate-risk group (15%–20%), very low-risk groups (<5%), or patients with dense breasts? These are challenges that could be met through novel and individualized approaches (for example, polygenic risk scoring, further research on newer modalities of screening [TABLE 8]), improved screening algorithms for persons with dense breasts, and enhanced clinician engagement to achieve universal breast cancer and BRCA risk assessment of patients by age 25 to 30.

In 2023, best practice and consensus guidelines for intermediate- and low-risk breast cancer groups remain unclear, and one of the many ongoing challenges is to further reduce the impact of breast cancer on the lives of persons affected and the recognized harms of SM.

In the meantime, there is consensus in average-risk patients to provide counseling about SM by age 40. My approach has been to counsel all average-risk patients on the risks and benefits of mammography using the acronym TIP-V:

  • Use a Tool to calculate breast cancer risk (TABLE 3). If they are at high risk, provide recommendations for high-risk management (TABLE 7).7
  • For average-risk patients, counsel that their Incidence of developing breast cancer in the next decade is approximately 1 in 70 (TABLE 6).4
  • Provide data and guidance on the benefits of SM for patients in their 40s (mortality improvement, decreased treatment) and the likelihood of harm from breast cancer screening (10% callback, 1% benign biopsy, and <1% likelihood of overdiagnosis [TABLE 4]).4,14,15
  • Engage the patient to better understand their relative Values of the benefits and harms and make a shared decision on screening starting at age 40, 45, or 50.
 

Looking forward

In summary, SM remains an important tool in the effort to decrease the risk of mortality due to breast cancer. Given the limitations of SM, however, newer tools and methods—abbreviated MRI, contrast-enhanced mammography, molecular breast imaging, customized screening intervals depending on individual risk/polygenic risk score, and customized counseling and screening based on risk factors (TABLES 2 and 7)—will play an increased role in recommendations for breast cancer screening in the future. ●

References
  1. Giaquinto AN, Sung H, Miller KD, et al. Breast cancer statistics, 2022. CA Cancer J Clin. 2022;72:524-541.
  2. Berry DA, Cronin KA, Plevritis SK, et al. Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med. 2005;353:1784-1792.
  3. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209-249.
  4. Oeffinger KC, Fontham ET, Etzioni R, et al; American Cancer Society. Breast cancer screening for women at average risk: 2015 guideline update from the American Cancer Society. JAMA. 2015;314:1599-1614.
  5. US Preventive Services Task Force; Owens DK, Davidson KW, Drist AH, et al. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer: US Preventive Services Task Force Recommendation statement. JAMA. 2019;322:652-665.
  6. Nelson HD, Cantor A, Humphrey L, et al. Screening for breast cancer: a systematic review to update the 2009 US Preventive Services Task Force recommendation. Evidence synthesis no 124.  AHRQ publication no 14-05201-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2016.
  7. Bevers TB, Helvie M, Bonaccio E, et al. Breast cancer screening and diagnosis, version 3.2018, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2018;16:1362-1389.
  8. Duffy SW, Vulkan D, Cuckle H, et al. Effect of mammographic screening from age 40 years on breast cancer mortality (UK Age trial): final results of a randomised, controlled trial. Lancet Oncol. 2020;21:1165-1172.
  9. Karzai S, Port E, Siderides C, et al. Impact of screening mammography on treatment in young women diagnosed with breast cancer. Ann Surg Oncol. 2022. doi:10.1245/ s10434-022-11581-6.
  10. Ahn S, Wooster M, Valente C, et al. Impact of screening mammography on treatment in women diagnosed with breast cancer. Ann Surg Oncol. 2018;25:2979-2986.
  11. Coldman A, Phillips N. Incidence of breast cancer and estimates of overdiagnosis after the initiation of a population-based mammography screening program. CMAJ. 2013;185:E492-E498.
  12. Etzioni R, Gulati R, Mallinger L, et al. Influence of study features and methods on overdiagnosis estimates in breast and prostate cancer screening. Ann Internal Med. 2013;158:831-838.
  13. Ryser MD, Lange J, Inoue LY, et al. Estimation of breast cancer overdiagnosis in a US breast screening cohort. Ann Intern Med. 2022;175:471-478.
  14. Monticciolo DL, Malak SF, Friedewald SM, et al. Breast cancer screening recommendations inclusive of all women at average risk: update from the ACR and Society of Breast Imaging. J Am Coll Radiol. 2021;18:1280-1288.
  15. Nelson HD, Fu R, Cantor A, Pappas M, et al. Effectiveness of breast cancer screening: systematic review and meta-analysis to update the 2009 US Preventive Services Task Force recommendation. Ann Internal Med. 2016;164:244-255.
  16. Hendrick RE, Helvie MA, Hardesty LA. Implications of CISNET modeling on number needed to screen and mortality reduction with digital mammography in women 40–49 years old. Am J Roentgenol. 2014;203:1379-1381.
  17. Broeders M, Moss S, Nyström L, et al; EUROSCREEN Working Group. The impact of mammographic screening on breast cancer mortality in Europe: a review of observational studies. J Med Screen. 2012;19(suppl 1):14-25.
  18. Tabár L, Yen AMF, Wu WYY, et al. Insights from the breast cancer screening trials: how screening affects the natural history of breast cancer and implications for evaluating service screening programs. Breast J. 2015;21:13-20.
  19. Kriege M, Brekelmans CTM, Boetes C, et al; Magnetic Resonance Imaging Screening Study Group. 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.
  20. Vreemann S, Gubern-Merida A, Lardenoije S, et al. The frequency of missed breast cancers in women participating in a high-risk MRI screening program. Breast Cancer Res Treat. 2018;169:323-331.
  21. Bakker MF, de Lange SV, Pijnappel RM, et al. Supplemental MRI screening for women with extremely dense breast tissue. N Engl J Med. 2019;381:2091-2102.
  22. Amirikia KC, Mills P, Bush J, et al. Higher population‐based incidence rates of triple‐negative breast cancer among young African‐American women: implications for breast cancer screening recommendations. Cancer. 2011;117:2747-2753.
  23. Kohler BA, Sherman RL, Howlader N, et al. Annual report to the nation on the status of cancer, 1975-2011, featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state. J Natl Cancer Inst. 2015;107:djv048.
  24. Newman LA, Kaljee LM. Health disparities and triple-negative breast cancer in African American women: a review. JAMA Surg. 2017;152:485-493.
  25. Stapleton SM, Oseni TO, Bababekov YJ, et al. Race/ethnicity and age distribution of breast cancer diagnosis in the United States. JAMA Surg. 2018;153:594-595.
  26. Hendrick RE, Monticciolo DL, Biggs KW, et al. Age distributions of breast cancer diagnosis and mortality by race and ethnicity in US women. Cancer. 2021;127:4384-4392.
  27. Perry H, Fang AJ, Tsai EM, et al. Imaging health and radiology care of transgender patients: a call to build evidence-based best practices. J Am Coll Radiol. 2021;18(3 pt B):475-480.
  28. Lockhart R, Kamaya A. Patient-friendly summary of the ACR Appropriateness Criteria: transgender breast cancer screening. J Am Coll Radiol. 2022;19:e19.
  29. Expert Panel on Breast Imaging; Brown A, Lourenco AP, Niell BL, et al. ACR Appropriateness Criteria transgender breast cancer screening. J Am Coll Radiol. 2021;18:S502-S515.
  30. Mørch LS, Skovlund CW, Hannaford PC, et al. Contemporary hormonal contraception and the risk of breast cancer. N Engl J Med. 2017;377:2228-2239.
  31. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA Cancer J Clin. 2021;71:7-33.
  32. Laws A, Katlin F, Hans M, et al. Screening MRI does not increase cancer detection or result in an earlier stage at diagnosis for patients with high-risk breast lesions: a propensity score analysis. Ann Surg Oncol. 2023;30;68-77.
  33. American College of Obstetricians and Gynecologists. Practice bulletin no 179: Breast cancer risk assessment and screening in average-risk women. Obstet Gynecol. 2017;130:e1-e16.
  34. Grimm LJ, Mango VL, Harvey JA, et al. Implementation of abbreviated breast MRI for screening: AJR expert panel narrative review. AJR Am J Roentgenol. 2022;218:202-212.
  35. Potsch N, Vatteroini G, Clauser P, et al. Contrast-enhanced mammography versus contrast-enhanced breast MRI: a systematic review and meta-analysis. Radiology. 2022;305:94-103.
  36. Covington MF, Parent EE, Dibble EH, et al. Advances and future directions in molecular breast imaging. J Nucl Med. 2022;63:17-21.
Article PDF
obgm03502033_pearlman_0223.pdf
Author and Disclosure Information

Disclaimer: Gender-neutral terms (“persons,” “people,” “patients,” “individuals,” “they,” etc) are used throughout this article, but the use of screening mammography and other breast cancer screening tools generally references persons who were assigned female sex at birth.

Dr. Pearlman is Professor Emeritus, 
Departments of Obstetrics and 
Gynecology, Department of Surgery, 
University of Michigan Health 
System, Ann Arbor, Michigan.

The author reports no financial relationships relevant to  this article.

Issue
OBG Management - 35(2)
Publications
MDedge ObGyn
OBG Management
MDedge Hematology and Oncology
Federal Practitioner
AVAHO
Breast Cancer ICYMI
Topics
Breast Cancer
Page Number
33-44
Sections
Clinical Review
Author(s)
Mark D. Pearlman, MD
Author(s)
Mark D. Pearlman, MD
Author and Disclosure Information

Disclaimer: Gender-neutral terms (“persons,” “people,” “patients,” “individuals,” “they,” etc) are used throughout this article, but the use of screening mammography and other breast cancer screening tools generally references persons who were assigned female sex at birth.

Dr. Pearlman is Professor Emeritus, 
Departments of Obstetrics and 
Gynecology, Department of Surgery, 
University of Michigan Health 
System, Ann Arbor, Michigan.

The author reports no financial relationships relevant to  this article.

Author and Disclosure Information

Disclaimer: Gender-neutral terms (“persons,” “people,” “patients,” “individuals,” “they,” etc) are used throughout this article, but the use of screening mammography and other breast cancer screening tools generally references persons who were assigned female sex at birth.

Dr. Pearlman is Professor Emeritus, 
Departments of Obstetrics and 
Gynecology, Department of Surgery, 
University of Michigan Health 
System, Ann Arbor, Michigan.

The author reports no financial relationships relevant to  this article.

Article PDF
obgm03502033_pearlman_0223.pdf
Article PDF
obgm03502033_pearlman_0223.pdf

 

Meaningful progress has been made in reducing deaths due to breast cancer over the last half century, with a 43% decrease in mortality rate (breast cancer deaths per 100,000 population).1 Screening mammography (SM) has contributed greatly to that success, accounting for 30% to 70% of the reduced mortality rate, with the remainder due to advancements in breast cancer treatment.2 Despite these improvements, invasive breast cancer remains the highest incident cancer in the United States and in the world, is the second leading cause of cancer death in the United States, and results in more years of life lost than any other cancer (TABLE 1).1,3

While the benefits and harms of SM are reasonably well understood, different guidelines groups have approached the relative value of the risks and benefits differently, which has led to challenges in implementation of shared decision making, particularly around the age to initiate routine screening.4-6 In this article, we will focus on the data behind the controversy, current gaps in knowledge, challenges related to breast density and screening in diverse groups, and emerging technologies to address these gaps and provide a construct for appropriate counseling of the patient across the risk spectrum.

New series on cancer screening

In recognition of 35 years of publication of OBG Management, this article on breast cancer screening by Mark D. Pearlman, MD, kicks off a series that focuses on various cancer screening modalities and expert recommendations.

Stay tuned for articles on the future of cervical cancer screening and genetic testing for cancer risk beyond BRCA testing.

We look forward to continuing OBG Management’s mission of enhancing the quality of reproductive health care and the professional development of ObGyns and all women’s health care clinicians.

 

Breast cancer risk

Variables that affect risk

While female sex and older age are the 2 greatest risks for the development of breast cancer, many other factors can either increase or decrease breast cancer risk in a person’s lifetime. The importance of identifying risk factors is 3-fold:

  1. to perform risk assessment to determine if individuals would benefit from average-risk versus high-risk breast cancer surveillance
  2. to identify persons who might benefit from BRCA genetic counseling and screening, risk reduction medications or procedures, and
  3. to allow patients to determine whether any modification in their lifestyle or reproductive choices would make sense to them to reduce their future breast cancer risk.

Most of these risk variables are largely inalterable (for example, family history of breast cancer, carriage of genetic pathogenic variants such as BRCA1 and BRCA2, age of menarche and menopause), but some are potentially modifiable, such as parity, age at first birth, lactation and duration, and dietary factors, among others. TABLE 2 lists common breast cancer risk factors.

Breast cancer risk assessment

Several validated tools have been developed to estimate a person’s breast cancer risk (TABLE 3). These tools combine known risk factors and, depending on the specific tool, can provide estimates of 5-year, 10-year, or lifetime risk of breast cancer. Patients at highest risk can benefit from earlier screening, supplemental screening with breast magnetic resonance imaging (MRI), or risk reduction (see the section, “High-risk screening”). Ideally, a risk assessment should be done by age 30 so that patients at high risk can be identified for earlier or more intensive screening and for possible genetic testing in those at risk for carriage of the BRCA or other breast cancer gene pathogenic variants.5,7

Continue to: Breast cancer screening: Efficacy and harms...

 

 

Breast cancer screening: Efficacy and harms

The earliest studies of breast cancer screening with mammography were randomized controlled trials (RCTs) that compared screened and unscreened patients aged 40 to 74. Nearly all the RCTs and numerous well-designed incidence-based and case-control studies have demonstrated that SM results in a clinically and statistically significant reduction in breast cancer mortality (TABLE 4).4,6,8 Since the mid-1980s and continuing to the current day, SM programs are routinely recommended in the United States. In addition to the mortality benefit outlined in TABLE 4, SM also is associated with a need for less invasive treatments if breast cancer is diagnosed.9,10

With several decades of experience, SM programs have demonstrated that multiple harms are associated with SM, including callbacks, false-positive mammograms that result in a benign biopsy, and overdiagnosis of breast cancer (TABLE 4). Overdiagnosis is a mammographic detection of a breast cancer that would not have harmed that woman in her lifetime. Overdiagnosis leads to overtreatment of breast cancers with its attendant side effects, the emotional harms of a breast cancer diagnosis, and the substantial financial cost of cancer treatment. Estimates of overdiagnosis range from 0% to 50%, with the most likely estimate of invasive breast cancer overdiagnosis from SM between 5% and 15%.11-13 Some of these overdiagnosed cancers are due to very slow growing cancers or breast cancers that may even regress. However, the higher rates of overdiagnosis occur in older persons who are screened and in whom competing causes of mortality become more prevalent. It is estimated that overdiagnosis of invasive breast cancer in patients younger than age 60 is less than 1%, but it exceeds 14% in those older than age 80 (TABLE 4).14

A structured approach is needed to counsel patients about SM so that they understand both the substantial benefit (earlier-stage diagnosis, reduced need for treatment, reduced breast cancer and all-cause mortality) and the potential harms (callback, false-positive results, and overdiagnosis). Moreover, the relative balance of the benefits and harms are influenced throughout their lifetime by both aging and changes in their personal and family medical history.

 


Counseling should consider factors beyond just the performance of mammography (sensitivity and specificity), such as the patient’s current health and age (competing causes of mortality), likelihood of developing breast cancer based on risk assessment (more benefit in higher-risk persons), and the individual patient’s values on the importance of the benefits and harms. The differing emphases on mammography performance and the relative value of the benefits and harms have led experts to produce disparate national guideline recommendations (TABLE 5).

Should SM start at age 40, 45, or 50 in average-risk persons?

There is not clear consensus about the age at which to begin to recommend routine SM in patients at average risk. The National Comprehensive Cancer Network (NCCN),7 American Cancer Society (ACS),4 and the US Preventive Services Task Force (USPSTF)5 recommend that those at average risk start SM at age 40, 45, and 50, respectively (TABLE 5). While the guideline groups listed in TABLE 5 agree that there is level 1 evidence that SM reduces breast cancer mortality in the general population for persons starting at age 40, because the incidence of breast cancer is lower in younger persons (TABLE 6),4 the net population-based screening benefit is lower in this group, and the number needed to invite to screening to save a single life due to breast cancer varies.

For patients in their 40s, it is estimated that 1,904 individuals need to be invited to SM to save 1 life, whereas for patients in their 50s, it is 1,339.15 However, for patients in their 40s, the number needed to screen to save 1 life due to breast cancer decreases from 1 in 1,904 if invited to be screened to 1 in 588 if they are actually screened.16 Furthermore, if a patient is diagnosed with breast cancer at age 40–50, the likelihood of dying is reduced at least 22% and perhaps as high as 48% if her cancer was diagnosed on SM compared with an unscreened individual with a symptomatic presentation (for example, palpable mass).4,15,17,18 Another benefit of SM in the fifth decade of life (40s) is the decreased need for more extensive treatment, including a higher risk of need for chemotherapy (odds ratio [OR], 2.81; 95% confidence interval [CI], 1.16–6.84); need for mastectomy (OR, 3.41; 95% CI, 1.36–8.52); and need for axillary lymph node dissection (OR, 5.76; 95% CI, 2.40–13.82) in unscreened (compared with screened) patients diagnosed with breast cancer.10

The harms associated with SM are not inconsequential and include callbacks (approximately 1 in 10), false-positive biopsy (approximately 1 in 100), and overdiagnosis (likely <1% of all breast cancers in persons younger than age 50). Because most patients in their 40s will not develop breast cancer (TABLE 6), the benefit of reduced breast cancer mortality will not be experienced by most in this decade of life, but they are still just as likely to experience a callback, false-positive biopsy, or the possibility of overdiagnosis. Interpretation of this balance on a population level is the crux of the various guideline groups’ development of differing recommendations as to when screening should start. Despite this seeming disagreement, all the guideline groups listed in TABLE 5 concur that persons at average risk for breast cancer should be offered SM if they desire starting at age 40 after a shared decision-making conversation that incorporates the patient’s view on the relative value of the benefits and risks.

Continue to: High-risk screening...

 

 

High-risk screening

Unlike in screening average-risk patients, there is less disagreement about screening in high-risk groups. TABLE 7 outlines the various categories and recommended strategies that qualify for screening at younger ages or more intensive screening. Adding breast MRI to SM in high-risk individuals results in both higher cancer detection rates and less interval breast cancers (cancers diagnosed between screening rounds) diagnosed compared with SM alone.19,20 Interval breast cancer tends to be more aggressive and is used as a surrogate marker for more recognized factors, such as breast cancer mortality. In addition to less interval breast cancers, high-risk patients are more likely to be diagnosed with node-negative disease if screening breast MRI is added to SM.

Long-term mortality benefit studies using MRI have not been conducted due to the prolonged follow-up times needed. Expense, lower specificity compared with mammography (that is, more false-positive results), and need for the use of gadolinium limit more widespread use of breast MRI screening in average-risk persons.

 

Screening in patients with dense breasts

Half of patients undergoing SM in the United States have dense breasts (heterogeneously dense breasts, 40%; extremely dense breasts, 10%). Importantly, increasing breast density is associated with a lower cancer detection rate with SM and is an independent risk factor for developing breast cancer. While most states already require patients to be notified if they have dense breasts identified on SM, the US Food and Drug Administration will soon make breast density patient notification a national standard (see: https://delauro.house.gov/media-center/press-releases/delauro-secures-timeline-fda-rollout-breast-density-notification-rule).

Most of the risk assessment tools listed in TABLE 3 incorporate breast density into their calculation of breast cancer risk. If that calculation places a patient into one of the highest-risk groups (based on additional factors like strong family history of breast cancer, reproductive risk factors, BRCA carriage, and so on), more intensive surveillance should be recommended (TABLE 7).7 However, once these risk calculations are done, most persons with dense breasts will remain in an average-risk category.

Because of the frequency and risks associated with dense breasts, different and alternative strategies have been recommended for screening persons who are at average risk with dense breasts. Supplemental screening with MRI, ultrasonography, contrast-enhanced mammography, and molecular breast imaging are all being considered but have not been studied sufficiently to demonstrate mortality benefit or cost-effectiveness.

Of all the supplemental modalities used to screen patients with dense breasts, MRI has been the best studied. A large RCT in the Netherlands evaluated supplemental MRI screening in persons with extremely dense breasts after a negative mammogram.21 Compared with no supplemental screening, the MRI group had 17 additional cancers detected per 1,000 screened and a 50% reduction in interval breast cancers; in addition, MRI was associated with a positive predictive value of 26% for biopsies. At present, high cost and limited access to standard breast MRI has not allowed its routine use for persons with dense breasts in the United States, but this may change with more experience and more widespread introduction and experience with abbreviated (or rapid) breast MRI in the future (TABLE 8).

Equitable screening

Black persons who are diagnosed with breast cancer have a 40% higher risk of dying than White patients due to multiple factors, including systemic racial factors (implicit and unconscious bias), reduced access to care, and a lower likelihood of receiving standard of care once diagnosed.22-24 In addition, Black patients have twice the likelihood of being diagnosed with triple-negative breast cancers, a biologically more aggressive tumor.22-24 Among Black, Asian, and Hispanic persons diagnosed with breast cancer, one-third are diagnosed younger than age 50, which is higher than for non-Hispanic White persons. Prior to the age of 50, Black, Asian, and Hispanic patients also have a 72% more likelihood of being diagnosed with invasive breast cancer, have a 58% greater risk of advanced-stage disease, and have a 127% higher risk of dying from breast cancer compared with White patients.25,26 Based on all of these factors, delaying SM until age 50 may adversely affect the Black, Asian, and Hispanic populations.

Persons in the LGBTQ+ community do not present for SM as frequently as the general population, often because they feel threatened or unwelcome.27 Clinicians and breast imaging units should review their inclusivity policies and training to provide a welcoming and respectful environment to all persons in an effort to reduce these barriers. While data are limited and largely depend on expert opinion, current recommendations for screening in the transgender patient depend on sex assigned at birth, the type and duration of hormone use, and surgical history. In patients assigned female sex at birth, average-risk and high-risk screening recommendations are similar to those for the general population unless bilateral mastectomy has been performed.28 In transfeminine patients who have used hormones for longer than 5 years, some groups recommend annual screening starting at age 40, although well-designed studies are lacking.29

Continue to: We have done well, can we do better?...

 

 

We have done well, can we do better?

Screening mammography clearly has been an important and effective tool in the effort to reduce breast cancer mortality, but there are clear limitations. These include moderate sensitivity of mammography, particularly in patients with dense breasts, and a specificity that results in either callbacks (10%), breast biopsies for benign disease (1%), or the reality of overdiagnosis, which becomes increasingly important in older patients.

With the introduction of mammography in the mid-1980s, a one-size-fits-all approach has proved challenging more recently due to an increased recognition of the harms of screening. As a result of this evolving understanding, different recommendations for average-risk screening have emerged. With the advent of breast MRI, risk-based screening is an important but underutilized tool to identify highest-risk individuals, which is associated with improved cancer detection rates, reduced node-positive disease, and fewer diagnosed interval breast cancers. Assuring that nearly all of this highest-risk group is identified through routine breast cancer risk assessment remains a challenge for clinicians.

But what SM recommendations should be offered to persons who fall into an intermediate-risk group (15%–20%), very low-risk groups (<5%), or patients with dense breasts? These are challenges that could be met through novel and individualized approaches (for example, polygenic risk scoring, further research on newer modalities of screening [TABLE 8]), improved screening algorithms for persons with dense breasts, and enhanced clinician engagement to achieve universal breast cancer and BRCA risk assessment of patients by age 25 to 30.

In 2023, best practice and consensus guidelines for intermediate- and low-risk breast cancer groups remain unclear, and one of the many ongoing challenges is to further reduce the impact of breast cancer on the lives of persons affected and the recognized harms of SM.

In the meantime, there is consensus in average-risk patients to provide counseling about SM by age 40. My approach has been to counsel all average-risk patients on the risks and benefits of mammography using the acronym TIP-V:

  • Use a Tool to calculate breast cancer risk (TABLE 3). If they are at high risk, provide recommendations for high-risk management (TABLE 7).7
  • For average-risk patients, counsel that their Incidence of developing breast cancer in the next decade is approximately 1 in 70 (TABLE 6).4
  • Provide data and guidance on the benefits of SM for patients in their 40s (mortality improvement, decreased treatment) and the likelihood of harm from breast cancer screening (10% callback, 1% benign biopsy, and <1% likelihood of overdiagnosis [TABLE 4]).4,14,15
  • Engage the patient to better understand their relative Values of the benefits and harms and make a shared decision on screening starting at age 40, 45, or 50.
 

Looking forward

In summary, SM remains an important tool in the effort to decrease the risk of mortality due to breast cancer. Given the limitations of SM, however, newer tools and methods—abbreviated MRI, contrast-enhanced mammography, molecular breast imaging, customized screening intervals depending on individual risk/polygenic risk score, and customized counseling and screening based on risk factors (TABLES 2 and 7)—will play an increased role in recommendations for breast cancer screening in the future. ●

 

Meaningful progress has been made in reducing deaths due to breast cancer over the last half century, with a 43% decrease in mortality rate (breast cancer deaths per 100,000 population).1 Screening mammography (SM) has contributed greatly to that success, accounting for 30% to 70% of the reduced mortality rate, with the remainder due to advancements in breast cancer treatment.2 Despite these improvements, invasive breast cancer remains the highest incident cancer in the United States and in the world, is the second leading cause of cancer death in the United States, and results in more years of life lost than any other cancer (TABLE 1).1,3

While the benefits and harms of SM are reasonably well understood, different guidelines groups have approached the relative value of the risks and benefits differently, which has led to challenges in implementation of shared decision making, particularly around the age to initiate routine screening.4-6 In this article, we will focus on the data behind the controversy, current gaps in knowledge, challenges related to breast density and screening in diverse groups, and emerging technologies to address these gaps and provide a construct for appropriate counseling of the patient across the risk spectrum.

New series on cancer screening

In recognition of 35 years of publication of OBG Management, this article on breast cancer screening by Mark D. Pearlman, MD, kicks off a series that focuses on various cancer screening modalities and expert recommendations.

Stay tuned for articles on the future of cervical cancer screening and genetic testing for cancer risk beyond BRCA testing.

We look forward to continuing OBG Management’s mission of enhancing the quality of reproductive health care and the professional development of ObGyns and all women’s health care clinicians.

 

Breast cancer risk

Variables that affect risk

While female sex and older age are the 2 greatest risks for the development of breast cancer, many other factors can either increase or decrease breast cancer risk in a person’s lifetime. The importance of identifying risk factors is 3-fold:

  1. to perform risk assessment to determine if individuals would benefit from average-risk versus high-risk breast cancer surveillance
  2. to identify persons who might benefit from BRCA genetic counseling and screening, risk reduction medications or procedures, and
  3. to allow patients to determine whether any modification in their lifestyle or reproductive choices would make sense to them to reduce their future breast cancer risk.

Most of these risk variables are largely inalterable (for example, family history of breast cancer, carriage of genetic pathogenic variants such as BRCA1 and BRCA2, age of menarche and menopause), but some are potentially modifiable, such as parity, age at first birth, lactation and duration, and dietary factors, among others. TABLE 2 lists common breast cancer risk factors.

Breast cancer risk assessment

Several validated tools have been developed to estimate a person’s breast cancer risk (TABLE 3). These tools combine known risk factors and, depending on the specific tool, can provide estimates of 5-year, 10-year, or lifetime risk of breast cancer. Patients at highest risk can benefit from earlier screening, supplemental screening with breast magnetic resonance imaging (MRI), or risk reduction (see the section, “High-risk screening”). Ideally, a risk assessment should be done by age 30 so that patients at high risk can be identified for earlier or more intensive screening and for possible genetic testing in those at risk for carriage of the BRCA or other breast cancer gene pathogenic variants.5,7

Continue to: Breast cancer screening: Efficacy and harms...

 

 

Breast cancer screening: Efficacy and harms

The earliest studies of breast cancer screening with mammography were randomized controlled trials (RCTs) that compared screened and unscreened patients aged 40 to 74. Nearly all the RCTs and numerous well-designed incidence-based and case-control studies have demonstrated that SM results in a clinically and statistically significant reduction in breast cancer mortality (TABLE 4).4,6,8 Since the mid-1980s and continuing to the current day, SM programs are routinely recommended in the United States. In addition to the mortality benefit outlined in TABLE 4, SM also is associated with a need for less invasive treatments if breast cancer is diagnosed.9,10

With several decades of experience, SM programs have demonstrated that multiple harms are associated with SM, including callbacks, false-positive mammograms that result in a benign biopsy, and overdiagnosis of breast cancer (TABLE 4). Overdiagnosis is a mammographic detection of a breast cancer that would not have harmed that woman in her lifetime. Overdiagnosis leads to overtreatment of breast cancers with its attendant side effects, the emotional harms of a breast cancer diagnosis, and the substantial financial cost of cancer treatment. Estimates of overdiagnosis range from 0% to 50%, with the most likely estimate of invasive breast cancer overdiagnosis from SM between 5% and 15%.11-13 Some of these overdiagnosed cancers are due to very slow growing cancers or breast cancers that may even regress. However, the higher rates of overdiagnosis occur in older persons who are screened and in whom competing causes of mortality become more prevalent. It is estimated that overdiagnosis of invasive breast cancer in patients younger than age 60 is less than 1%, but it exceeds 14% in those older than age 80 (TABLE 4).14

A structured approach is needed to counsel patients about SM so that they understand both the substantial benefit (earlier-stage diagnosis, reduced need for treatment, reduced breast cancer and all-cause mortality) and the potential harms (callback, false-positive results, and overdiagnosis). Moreover, the relative balance of the benefits and harms are influenced throughout their lifetime by both aging and changes in their personal and family medical history.

 


Counseling should consider factors beyond just the performance of mammography (sensitivity and specificity), such as the patient’s current health and age (competing causes of mortality), likelihood of developing breast cancer based on risk assessment (more benefit in higher-risk persons), and the individual patient’s values on the importance of the benefits and harms. The differing emphases on mammography performance and the relative value of the benefits and harms have led experts to produce disparate national guideline recommendations (TABLE 5).

Should SM start at age 40, 45, or 50 in average-risk persons?

There is not clear consensus about the age at which to begin to recommend routine SM in patients at average risk. The National Comprehensive Cancer Network (NCCN),7 American Cancer Society (ACS),4 and the US Preventive Services Task Force (USPSTF)5 recommend that those at average risk start SM at age 40, 45, and 50, respectively (TABLE 5). While the guideline groups listed in TABLE 5 agree that there is level 1 evidence that SM reduces breast cancer mortality in the general population for persons starting at age 40, because the incidence of breast cancer is lower in younger persons (TABLE 6),4 the net population-based screening benefit is lower in this group, and the number needed to invite to screening to save a single life due to breast cancer varies.

For patients in their 40s, it is estimated that 1,904 individuals need to be invited to SM to save 1 life, whereas for patients in their 50s, it is 1,339.15 However, for patients in their 40s, the number needed to screen to save 1 life due to breast cancer decreases from 1 in 1,904 if invited to be screened to 1 in 588 if they are actually screened.16 Furthermore, if a patient is diagnosed with breast cancer at age 40–50, the likelihood of dying is reduced at least 22% and perhaps as high as 48% if her cancer was diagnosed on SM compared with an unscreened individual with a symptomatic presentation (for example, palpable mass).4,15,17,18 Another benefit of SM in the fifth decade of life (40s) is the decreased need for more extensive treatment, including a higher risk of need for chemotherapy (odds ratio [OR], 2.81; 95% confidence interval [CI], 1.16–6.84); need for mastectomy (OR, 3.41; 95% CI, 1.36–8.52); and need for axillary lymph node dissection (OR, 5.76; 95% CI, 2.40–13.82) in unscreened (compared with screened) patients diagnosed with breast cancer.10

The harms associated with SM are not inconsequential and include callbacks (approximately 1 in 10), false-positive biopsy (approximately 1 in 100), and overdiagnosis (likely <1% of all breast cancers in persons younger than age 50). Because most patients in their 40s will not develop breast cancer (TABLE 6), the benefit of reduced breast cancer mortality will not be experienced by most in this decade of life, but they are still just as likely to experience a callback, false-positive biopsy, or the possibility of overdiagnosis. Interpretation of this balance on a population level is the crux of the various guideline groups’ development of differing recommendations as to when screening should start. Despite this seeming disagreement, all the guideline groups listed in TABLE 5 concur that persons at average risk for breast cancer should be offered SM if they desire starting at age 40 after a shared decision-making conversation that incorporates the patient’s view on the relative value of the benefits and risks.

Continue to: High-risk screening...

 

 

High-risk screening

Unlike in screening average-risk patients, there is less disagreement about screening in high-risk groups. TABLE 7 outlines the various categories and recommended strategies that qualify for screening at younger ages or more intensive screening. Adding breast MRI to SM in high-risk individuals results in both higher cancer detection rates and less interval breast cancers (cancers diagnosed between screening rounds) diagnosed compared with SM alone.19,20 Interval breast cancer tends to be more aggressive and is used as a surrogate marker for more recognized factors, such as breast cancer mortality. In addition to less interval breast cancers, high-risk patients are more likely to be diagnosed with node-negative disease if screening breast MRI is added to SM.

Long-term mortality benefit studies using MRI have not been conducted due to the prolonged follow-up times needed. Expense, lower specificity compared with mammography (that is, more false-positive results), and need for the use of gadolinium limit more widespread use of breast MRI screening in average-risk persons.

 

Screening in patients with dense breasts

Half of patients undergoing SM in the United States have dense breasts (heterogeneously dense breasts, 40%; extremely dense breasts, 10%). Importantly, increasing breast density is associated with a lower cancer detection rate with SM and is an independent risk factor for developing breast cancer. While most states already require patients to be notified if they have dense breasts identified on SM, the US Food and Drug Administration will soon make breast density patient notification a national standard (see: https://delauro.house.gov/media-center/press-releases/delauro-secures-timeline-fda-rollout-breast-density-notification-rule).

Most of the risk assessment tools listed in TABLE 3 incorporate breast density into their calculation of breast cancer risk. If that calculation places a patient into one of the highest-risk groups (based on additional factors like strong family history of breast cancer, reproductive risk factors, BRCA carriage, and so on), more intensive surveillance should be recommended (TABLE 7).7 However, once these risk calculations are done, most persons with dense breasts will remain in an average-risk category.

Because of the frequency and risks associated with dense breasts, different and alternative strategies have been recommended for screening persons who are at average risk with dense breasts. Supplemental screening with MRI, ultrasonography, contrast-enhanced mammography, and molecular breast imaging are all being considered but have not been studied sufficiently to demonstrate mortality benefit or cost-effectiveness.

Of all the supplemental modalities used to screen patients with dense breasts, MRI has been the best studied. A large RCT in the Netherlands evaluated supplemental MRI screening in persons with extremely dense breasts after a negative mammogram.21 Compared with no supplemental screening, the MRI group had 17 additional cancers detected per 1,000 screened and a 50% reduction in interval breast cancers; in addition, MRI was associated with a positive predictive value of 26% for biopsies. At present, high cost and limited access to standard breast MRI has not allowed its routine use for persons with dense breasts in the United States, but this may change with more experience and more widespread introduction and experience with abbreviated (or rapid) breast MRI in the future (TABLE 8).

Equitable screening

Black persons who are diagnosed with breast cancer have a 40% higher risk of dying than White patients due to multiple factors, including systemic racial factors (implicit and unconscious bias), reduced access to care, and a lower likelihood of receiving standard of care once diagnosed.22-24 In addition, Black patients have twice the likelihood of being diagnosed with triple-negative breast cancers, a biologically more aggressive tumor.22-24 Among Black, Asian, and Hispanic persons diagnosed with breast cancer, one-third are diagnosed younger than age 50, which is higher than for non-Hispanic White persons. Prior to the age of 50, Black, Asian, and Hispanic patients also have a 72% more likelihood of being diagnosed with invasive breast cancer, have a 58% greater risk of advanced-stage disease, and have a 127% higher risk of dying from breast cancer compared with White patients.25,26 Based on all of these factors, delaying SM until age 50 may adversely affect the Black, Asian, and Hispanic populations.

Persons in the LGBTQ+ community do not present for SM as frequently as the general population, often because they feel threatened or unwelcome.27 Clinicians and breast imaging units should review their inclusivity policies and training to provide a welcoming and respectful environment to all persons in an effort to reduce these barriers. While data are limited and largely depend on expert opinion, current recommendations for screening in the transgender patient depend on sex assigned at birth, the type and duration of hormone use, and surgical history. In patients assigned female sex at birth, average-risk and high-risk screening recommendations are similar to those for the general population unless bilateral mastectomy has been performed.28 In transfeminine patients who have used hormones for longer than 5 years, some groups recommend annual screening starting at age 40, although well-designed studies are lacking.29

Continue to: We have done well, can we do better?...

 

 

We have done well, can we do better?

Screening mammography clearly has been an important and effective tool in the effort to reduce breast cancer mortality, but there are clear limitations. These include moderate sensitivity of mammography, particularly in patients with dense breasts, and a specificity that results in either callbacks (10%), breast biopsies for benign disease (1%), or the reality of overdiagnosis, which becomes increasingly important in older patients.

With the introduction of mammography in the mid-1980s, a one-size-fits-all approach has proved challenging more recently due to an increased recognition of the harms of screening. As a result of this evolving understanding, different recommendations for average-risk screening have emerged. With the advent of breast MRI, risk-based screening is an important but underutilized tool to identify highest-risk individuals, which is associated with improved cancer detection rates, reduced node-positive disease, and fewer diagnosed interval breast cancers. Assuring that nearly all of this highest-risk group is identified through routine breast cancer risk assessment remains a challenge for clinicians.

But what SM recommendations should be offered to persons who fall into an intermediate-risk group (15%–20%), very low-risk groups (<5%), or patients with dense breasts? These are challenges that could be met through novel and individualized approaches (for example, polygenic risk scoring, further research on newer modalities of screening [TABLE 8]), improved screening algorithms for persons with dense breasts, and enhanced clinician engagement to achieve universal breast cancer and BRCA risk assessment of patients by age 25 to 30.

In 2023, best practice and consensus guidelines for intermediate- and low-risk breast cancer groups remain unclear, and one of the many ongoing challenges is to further reduce the impact of breast cancer on the lives of persons affected and the recognized harms of SM.

In the meantime, there is consensus in average-risk patients to provide counseling about SM by age 40. My approach has been to counsel all average-risk patients on the risks and benefits of mammography using the acronym TIP-V:

  • Use a Tool to calculate breast cancer risk (TABLE 3). If they are at high risk, provide recommendations for high-risk management (TABLE 7).7
  • For average-risk patients, counsel that their Incidence of developing breast cancer in the next decade is approximately 1 in 70 (TABLE 6).4
  • Provide data and guidance on the benefits of SM for patients in their 40s (mortality improvement, decreased treatment) and the likelihood of harm from breast cancer screening (10% callback, 1% benign biopsy, and <1% likelihood of overdiagnosis [TABLE 4]).4,14,15
  • Engage the patient to better understand their relative Values of the benefits and harms and make a shared decision on screening starting at age 40, 45, or 50.
 

Looking forward

In summary, SM remains an important tool in the effort to decrease the risk of mortality due to breast cancer. Given the limitations of SM, however, newer tools and methods—abbreviated MRI, contrast-enhanced mammography, molecular breast imaging, customized screening intervals depending on individual risk/polygenic risk score, and customized counseling and screening based on risk factors (TABLES 2 and 7)—will play an increased role in recommendations for breast cancer screening in the future. ●

References
  1. Giaquinto AN, Sung H, Miller KD, et al. Breast cancer statistics, 2022. CA Cancer J Clin. 2022;72:524-541.
  2. Berry DA, Cronin KA, Plevritis SK, et al. Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med. 2005;353:1784-1792.
  3. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209-249.
  4. Oeffinger KC, Fontham ET, Etzioni R, et al; American Cancer Society. Breast cancer screening for women at average risk: 2015 guideline update from the American Cancer Society. JAMA. 2015;314:1599-1614.
  5. US Preventive Services Task Force; Owens DK, Davidson KW, Drist AH, et al. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer: US Preventive Services Task Force Recommendation statement. JAMA. 2019;322:652-665.
  6. Nelson HD, Cantor A, Humphrey L, et al. Screening for breast cancer: a systematic review to update the 2009 US Preventive Services Task Force recommendation. Evidence synthesis no 124.  AHRQ publication no 14-05201-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2016.
  7. Bevers TB, Helvie M, Bonaccio E, et al. Breast cancer screening and diagnosis, version 3.2018, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2018;16:1362-1389.
  8. Duffy SW, Vulkan D, Cuckle H, et al. Effect of mammographic screening from age 40 years on breast cancer mortality (UK Age trial): final results of a randomised, controlled trial. Lancet Oncol. 2020;21:1165-1172.
  9. Karzai S, Port E, Siderides C, et al. Impact of screening mammography on treatment in young women diagnosed with breast cancer. Ann Surg Oncol. 2022. doi:10.1245/ s10434-022-11581-6.
  10. Ahn S, Wooster M, Valente C, et al. Impact of screening mammography on treatment in women diagnosed with breast cancer. Ann Surg Oncol. 2018;25:2979-2986.
  11. Coldman A, Phillips N. Incidence of breast cancer and estimates of overdiagnosis after the initiation of a population-based mammography screening program. CMAJ. 2013;185:E492-E498.
  12. Etzioni R, Gulati R, Mallinger L, et al. Influence of study features and methods on overdiagnosis estimates in breast and prostate cancer screening. Ann Internal Med. 2013;158:831-838.
  13. Ryser MD, Lange J, Inoue LY, et al. Estimation of breast cancer overdiagnosis in a US breast screening cohort. Ann Intern Med. 2022;175:471-478.
  14. Monticciolo DL, Malak SF, Friedewald SM, et al. Breast cancer screening recommendations inclusive of all women at average risk: update from the ACR and Society of Breast Imaging. J Am Coll Radiol. 2021;18:1280-1288.
  15. Nelson HD, Fu R, Cantor A, Pappas M, et al. Effectiveness of breast cancer screening: systematic review and meta-analysis to update the 2009 US Preventive Services Task Force recommendation. Ann Internal Med. 2016;164:244-255.
  16. Hendrick RE, Helvie MA, Hardesty LA. Implications of CISNET modeling on number needed to screen and mortality reduction with digital mammography in women 40–49 years old. Am J Roentgenol. 2014;203:1379-1381.
  17. Broeders M, Moss S, Nyström L, et al; EUROSCREEN Working Group. The impact of mammographic screening on breast cancer mortality in Europe: a review of observational studies. J Med Screen. 2012;19(suppl 1):14-25.
  18. Tabár L, Yen AMF, Wu WYY, et al. Insights from the breast cancer screening trials: how screening affects the natural history of breast cancer and implications for evaluating service screening programs. Breast J. 2015;21:13-20.
  19. Kriege M, Brekelmans CTM, Boetes C, et al; Magnetic Resonance Imaging Screening Study Group. 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.
  20. Vreemann S, Gubern-Merida A, Lardenoije S, et al. The frequency of missed breast cancers in women participating in a high-risk MRI screening program. Breast Cancer Res Treat. 2018;169:323-331.
  21. Bakker MF, de Lange SV, Pijnappel RM, et al. Supplemental MRI screening for women with extremely dense breast tissue. N Engl J Med. 2019;381:2091-2102.
  22. Amirikia KC, Mills P, Bush J, et al. Higher population‐based incidence rates of triple‐negative breast cancer among young African‐American women: implications for breast cancer screening recommendations. Cancer. 2011;117:2747-2753.
  23. Kohler BA, Sherman RL, Howlader N, et al. Annual report to the nation on the status of cancer, 1975-2011, featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state. J Natl Cancer Inst. 2015;107:djv048.
  24. Newman LA, Kaljee LM. Health disparities and triple-negative breast cancer in African American women: a review. JAMA Surg. 2017;152:485-493.
  25. Stapleton SM, Oseni TO, Bababekov YJ, et al. Race/ethnicity and age distribution of breast cancer diagnosis in the United States. JAMA Surg. 2018;153:594-595.
  26. Hendrick RE, Monticciolo DL, Biggs KW, et al. Age distributions of breast cancer diagnosis and mortality by race and ethnicity in US women. Cancer. 2021;127:4384-4392.
  27. Perry H, Fang AJ, Tsai EM, et al. Imaging health and radiology care of transgender patients: a call to build evidence-based best practices. J Am Coll Radiol. 2021;18(3 pt B):475-480.
  28. Lockhart R, Kamaya A. Patient-friendly summary of the ACR Appropriateness Criteria: transgender breast cancer screening. J Am Coll Radiol. 2022;19:e19.
  29. Expert Panel on Breast Imaging; Brown A, Lourenco AP, Niell BL, et al. ACR Appropriateness Criteria transgender breast cancer screening. J Am Coll Radiol. 2021;18:S502-S515.
  30. Mørch LS, Skovlund CW, Hannaford PC, et al. Contemporary hormonal contraception and the risk of breast cancer. N Engl J Med. 2017;377:2228-2239.
  31. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA Cancer J Clin. 2021;71:7-33.
  32. Laws A, Katlin F, Hans M, et al. Screening MRI does not increase cancer detection or result in an earlier stage at diagnosis for patients with high-risk breast lesions: a propensity score analysis. Ann Surg Oncol. 2023;30;68-77.
  33. American College of Obstetricians and Gynecologists. Practice bulletin no 179: Breast cancer risk assessment and screening in average-risk women. Obstet Gynecol. 2017;130:e1-e16.
  34. Grimm LJ, Mango VL, Harvey JA, et al. Implementation of abbreviated breast MRI for screening: AJR expert panel narrative review. AJR Am J Roentgenol. 2022;218:202-212.
  35. Potsch N, Vatteroini G, Clauser P, et al. Contrast-enhanced mammography versus contrast-enhanced breast MRI: a systematic review and meta-analysis. Radiology. 2022;305:94-103.
  36. Covington MF, Parent EE, Dibble EH, et al. Advances and future directions in molecular breast imaging. J Nucl Med. 2022;63:17-21.
References
  1. Giaquinto AN, Sung H, Miller KD, et al. Breast cancer statistics, 2022. CA Cancer J Clin. 2022;72:524-541.
  2. Berry DA, Cronin KA, Plevritis SK, et al. Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med. 2005;353:1784-1792.
  3. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209-249.
  4. Oeffinger KC, Fontham ET, Etzioni R, et al; American Cancer Society. Breast cancer screening for women at average risk: 2015 guideline update from the American Cancer Society. JAMA. 2015;314:1599-1614.
  5. US Preventive Services Task Force; Owens DK, Davidson KW, Drist AH, et al. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer: US Preventive Services Task Force Recommendation statement. JAMA. 2019;322:652-665.
  6. Nelson HD, Cantor A, Humphrey L, et al. Screening for breast cancer: a systematic review to update the 2009 US Preventive Services Task Force recommendation. Evidence synthesis no 124.  AHRQ publication no 14-05201-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2016.
  7. Bevers TB, Helvie M, Bonaccio E, et al. Breast cancer screening and diagnosis, version 3.2018, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2018;16:1362-1389.
  8. Duffy SW, Vulkan D, Cuckle H, et al. Effect of mammographic screening from age 40 years on breast cancer mortality (UK Age trial): final results of a randomised, controlled trial. Lancet Oncol. 2020;21:1165-1172.
  9. Karzai S, Port E, Siderides C, et al. Impact of screening mammography on treatment in young women diagnosed with breast cancer. Ann Surg Oncol. 2022. doi:10.1245/ s10434-022-11581-6.
  10. Ahn S, Wooster M, Valente C, et al. Impact of screening mammography on treatment in women diagnosed with breast cancer. Ann Surg Oncol. 2018;25:2979-2986.
  11. Coldman A, Phillips N. Incidence of breast cancer and estimates of overdiagnosis after the initiation of a population-based mammography screening program. CMAJ. 2013;185:E492-E498.
  12. Etzioni R, Gulati R, Mallinger L, et al. Influence of study features and methods on overdiagnosis estimates in breast and prostate cancer screening. Ann Internal Med. 2013;158:831-838.
  13. Ryser MD, Lange J, Inoue LY, et al. Estimation of breast cancer overdiagnosis in a US breast screening cohort. Ann Intern Med. 2022;175:471-478.
  14. Monticciolo DL, Malak SF, Friedewald SM, et al. Breast cancer screening recommendations inclusive of all women at average risk: update from the ACR and Society of Breast Imaging. J Am Coll Radiol. 2021;18:1280-1288.
  15. Nelson HD, Fu R, Cantor A, Pappas M, et al. Effectiveness of breast cancer screening: systematic review and meta-analysis to update the 2009 US Preventive Services Task Force recommendation. Ann Internal Med. 2016;164:244-255.
  16. Hendrick RE, Helvie MA, Hardesty LA. Implications of CISNET modeling on number needed to screen and mortality reduction with digital mammography in women 40–49 years old. Am J Roentgenol. 2014;203:1379-1381.
  17. Broeders M, Moss S, Nyström L, et al; EUROSCREEN Working Group. The impact of mammographic screening on breast cancer mortality in Europe: a review of observational studies. J Med Screen. 2012;19(suppl 1):14-25.
  18. Tabár L, Yen AMF, Wu WYY, et al. Insights from the breast cancer screening trials: how screening affects the natural history of breast cancer and implications for evaluating service screening programs. Breast J. 2015;21:13-20.
  19. Kriege M, Brekelmans CTM, Boetes C, et al; Magnetic Resonance Imaging Screening Study Group. 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.
  20. Vreemann S, Gubern-Merida A, Lardenoije S, et al. The frequency of missed breast cancers in women participating in a high-risk MRI screening program. Breast Cancer Res Treat. 2018;169:323-331.
  21. Bakker MF, de Lange SV, Pijnappel RM, et al. Supplemental MRI screening for women with extremely dense breast tissue. N Engl J Med. 2019;381:2091-2102.
  22. Amirikia KC, Mills P, Bush J, et al. Higher population‐based incidence rates of triple‐negative breast cancer among young African‐American women: implications for breast cancer screening recommendations. Cancer. 2011;117:2747-2753.
  23. Kohler BA, Sherman RL, Howlader N, et al. Annual report to the nation on the status of cancer, 1975-2011, featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state. J Natl Cancer Inst. 2015;107:djv048.
  24. Newman LA, Kaljee LM. Health disparities and triple-negative breast cancer in African American women: a review. JAMA Surg. 2017;152:485-493.
  25. Stapleton SM, Oseni TO, Bababekov YJ, et al. Race/ethnicity and age distribution of breast cancer diagnosis in the United States. JAMA Surg. 2018;153:594-595.
  26. Hendrick RE, Monticciolo DL, Biggs KW, et al. Age distributions of breast cancer diagnosis and mortality by race and ethnicity in US women. Cancer. 2021;127:4384-4392.
  27. Perry H, Fang AJ, Tsai EM, et al. Imaging health and radiology care of transgender patients: a call to build evidence-based best practices. J Am Coll Radiol. 2021;18(3 pt B):475-480.
  28. Lockhart R, Kamaya A. Patient-friendly summary of the ACR Appropriateness Criteria: transgender breast cancer screening. J Am Coll Radiol. 2022;19:e19.
  29. Expert Panel on Breast Imaging; Brown A, Lourenco AP, Niell BL, et al. ACR Appropriateness Criteria transgender breast cancer screening. J Am Coll Radiol. 2021;18:S502-S515.
  30. Mørch LS, Skovlund CW, Hannaford PC, et al. Contemporary hormonal contraception and the risk of breast cancer. N Engl J Med. 2017;377:2228-2239.
  31. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA Cancer J Clin. 2021;71:7-33.
  32. Laws A, Katlin F, Hans M, et al. Screening MRI does not increase cancer detection or result in an earlier stage at diagnosis for patients with high-risk breast lesions: a propensity score analysis. Ann Surg Oncol. 2023;30;68-77.
  33. American College of Obstetricians and Gynecologists. Practice bulletin no 179: Breast cancer risk assessment and screening in average-risk women. Obstet Gynecol. 2017;130:e1-e16.
  34. Grimm LJ, Mango VL, Harvey JA, et al. Implementation of abbreviated breast MRI for screening: AJR expert panel narrative review. AJR Am J Roentgenol. 2022;218:202-212.
  35. Potsch N, Vatteroini G, Clauser P, et al. Contrast-enhanced mammography versus contrast-enhanced breast MRI: a systematic review and meta-analysis. Radiology. 2022;305:94-103.
  36. Covington MF, Parent EE, Dibble EH, et al. Advances and future directions in molecular breast imaging. J Nucl Med. 2022;63:17-21.
Issue
OBG Management - 35(2)
Issue
OBG Management - 35(2)
Page Number
33-44
Page Number
33-44
Publications
MDedge ObGyn
OBG Management
MDedge Hematology and Oncology
Federal Practitioner
AVAHO
Breast Cancer ICYMI
Publications
MDedge ObGyn
OBG Management
MDedge Hematology and Oncology
Federal Practitioner
AVAHO
Breast Cancer ICYMI
Topics
Breast Cancer
Article Type
Article
Sections
Clinical Review
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article
Teaser Media
Article PDF Media