Breast Cancer Screening in the Average-Risk Patient

Anatomy and Physiology

The mature adult breast comprises skin, subcutaneous tissue, and epithelial and stromal components. The epithelial component includes branching ducts that connect the structural and functional units of the breast, known as lobules, to the nipple. The stromal component, made up of fibrous and adipose tissue, constitutes the majority of the breast's volume in a non-lactating state.

Breast tissue extends vertically from the second to the sixth ribs and horizontally from the sternal edge to the midaxillary line. A portion of the breast tissue, known as the axillary tail of Spence, projects into the axilla. The skin of the breast is thin and contains sebaceous glands, exocrine sweat glands, and hair follicles. While the nipple lacks hair follicles, it is rich in sensory nerve endings and contains sebaceous and apocrine glands. The areola, which measures approximately 16 to 60 mm, is nearly circular and features increased pigmentation. Elevations near the periphery of the areola, known as Morgagni tubercles, form due to the openings of large sebaceous glands called Montgomery glands, which represent a transitional stage between sweat and mammary glands.

The breast is covered by superficial pectoral fascia, which extends into the superficial abdominal fascia of Camper. From beneath, the breast is encased in deep pectoral fascia, which covers the pectoralis major and serratus anterior muscles. These 2 fascial layers are interconnected by fibrous bands known as Cooper's suspensory ligaments, which provide natural support to the breasts. Most of the breast's blood supply comes from the internal mammary vessels. Sensory innervation primarily originates from the anterolateral and anteromedial branches of thoracic intercostal nerves T3 to T5. Lower fibers from the supraclavicular nerves of the cervical plexus also contribute to breast sensation.

Indications

The American Society of Breast Surgeons Screening Recommendations

The ASBrS guidelines recommend that all women aged 25 or older undergo a formal breast cancer risk assessment, with updates provided at appropriate intervals. Screening mammography should be discontinued when a woman's life expectancy is less than 10 years.

Women with an average risk of breast cancer and normal breast density should initiate yearly screening mammography, preferably 3-dimensional (3D) mammography, starting at age 40 without the need for supplemental imaging. For women with an average risk of breast cancer and heterogeneously or extremely dense breasts, yearly screening mammography, also preferably 3D, should start at age 40, with supplemental imaging considered.

Women at higher-than-average risk of breast cancer due to hereditary susceptibility from pathogenic mutation carrier status or prior chest wall radiation between the ages of 10 and 30 should begin yearly screening mammography at age 30 and be offered annual supplemental MRI starting at age 25. Additionally, women with a higher-than-average risk of breast cancer due to a predicted lifetime risk greater than 20% from any model or a strong family history should undergo yearly screening mammography and be offered annual supplemental MRI starting at age 35, as recommended by their clinician.

For women aged 50 or older with a prior history of breast cancer and non-dense breasts who did not undergo bilateral mastectomy, annual mammography, preferably 3D, is recommended. For women younger than 50 or those with dense breasts who have a prior history of breast cancer and did not undergo bilateral mastectomy, annual 3D mammography along with yearly supplemental MRI starting at age 35, as recommended by their clinician, is advised.

National Comprehensive Cancer Network Screening Recommendations

The 2024 NCCN Guidelines for Breast Cancer Screening and Diagnosis of Asymptomatic Average-Risk Patients include various recommendations (see Table 1. The 2024 NCCN Breast Cancer Screening Guidelines).[6]

Table 1. The 2024 NCCN Breast Cancer Screening Guidelines

Supplemental screening options such as breast MRI with and without contrast, abbreviated breast MRI, ultrasound, molecular breast imaging, or contrast-enhanced mammography can improve cancer detection rates but may also increase recall rates and lead to benign breast biopsies. For individuals at high risk of breast cancer, current evidence and the US Food and Drug Administration (FDA) safety announcement on gadolinium-based contrast agents support the continued recommendation for annual MRI in combination with annual screening mammography with tomosynthesis following shared decision-making.

For high-risk individuals who cannot undergo breast MRI, supplemental screening with contrast-enhanced mammography or molecular breast imaging is recommended. Whole breast ultrasound may be considered if contrast-enhanced or functional imaging is unavailable or inaccessible. Individuals with a residual lifetime breast cancer risk of 15% to 20% may be considered for supplemental screening based on individual risk factors. Abbreviated MRI demonstrates a higher cancer detection rate than mammography with tomosynthesis or ultrasound and likely offers similar sensitivity compared to a full diagnostic breast MRI protocol.

The NCCN panel recommends that women with average risk between the ages of 25 and 39 undergo a clinical assessment, risk-reduction counseling, and a clinical breast examination every 1 to 3 years. They should also be advised to notify their clinician immediately if they notice any changes in their breasts.[7]

American Cancer Society Screening Recommendations

The American Cancer Society (ACS) recommends the following breast cancer screening guidelines:

• Women with an average risk should undergo regular screening mammography starting at age 45.
• Women aged 45 to 54 should undergo annual screening.
• Women aged 55 and older can transition to biennial screening or continue annual screening.[8]
• Women aged 40 to 44 have the option to start annual mammography.
• Women aged 40 to 49 or older than 70 are not strongly recommended for routine screening.[9] However, in collaboration with mammography, breast MRI is considered an important screening modality for high-risk women and those with dense breasts.[5]
• Women who have up to 10 years of life expectancy and good health in general are advised to continue screening mammography.[10]

The United States Preventive Services Task Force Breast Cancer Screening Recommendations

The 2024 USPSTF Breast Cancer Screening guidelines represent the latest recommendations (see Table 2. The United States Preventive Services Task Force Breast Cancer Screening Recommendations).[3]

Table 2. The United States Preventive Services Task Force Breast Cancer Screening Recommendations

Notably, from 2016 to 2024, the USPSTF previously recommended biennial mammography for women aged 50 to 74. Screening was initially recommended for women aged 40 to 49 only after discussing and evaluating the risks and benefits of this test with their clinician.[7]

American College of Obstetricians and Gynecologists Screening Recommendations

ACOG released the age-based recommendations mentioned below for breast cancer risk assessment and screening in average-risk women, which were reaffirmed in 2021.

Patients aged 19 and older:

• Annual clinical breast examination.
• Breast self-awareness is encouraged to help detect palpable breast cancer; however, routine breast self-examinations are not recommended.

Patients aged 40 to 75:

• Screening mammography should be performed every 1 to 2 years. Women at average risk for breast cancer should undergo screening mammography every 1 or 2 years. This decision should be based on an informed, shared decision-making process that includes discussions about the benefits and harms of annual versus biennial screening, as well as the incorporation of patient values and preferences.
• Biennial screening mammography, especially for women aged 55 and older, is a reasonable option to minimize potential harm. However, patient counseling should emphasize that reducing the frequency of screening may also lead to a decrease in the benefits of early detection.
• Women at average risk of breast cancer should continue screening mammography until at least age 75. Decisions regarding the continuation or discontinuation of screening should not be based solely on age.

Patients aged 75 and older:

• The decision to discontinue screening mammography should be guided by a shared decision-making process that takes into account the woman's health status and life expectancy.
• While breast self-awareness can help detect palpable breast cancer and is encouraged, routine breast self-examinations are not recommended.

World Health Organization Screening Recommendations

In 2014, the WHO Position Paper on Mammography Screening outlined the below breast cancer screening guidelines.

• In well-resourced settings, organized population-based mammography screening programs are recommended for women aged 50 to 69 every 2 years. For women aged 40 to 49 and those aged 70 to 75, screening programs are suggested only if conducted within a framework of rigorous research, monitoring, and evaluation.
• In limited-resource settings with relatively strong health systems, organized population-based mammography screening programs are recommended for women aged 50 to 69, conducted every 2 years, provided the conditions for implementing such a program are met. The WHO advises against mammography screening for women aged 40 to 49 and those aged 70 to 75 in these settings.
• In limited-resource settings with weak health systems, organized population-based mammography screening programs may not be cost-effective or feasible. Prioritizing early diagnosis and prompt treatment for symptomatic women is essential. Clinical breast examinations appear to be a promising screening approach in these settings.[11]

Contraindications

The screening guidelines from various professional societies do not uniformly apply to the patient groups mentioned below.

• Patients with short life expectancy: This includes individuals with a minimal life expectancy due to other conditions (eg, hospice patients) for whom an asymptomatic breast cancer diagnosis would not significantly affect their expected lifespan.[9]

• Symptomatic patients: This includes individuals who present with new palpable breast masses, skin changes, or nipple discharge, requiring prompt diagnostic workup. These patients should be evaluated at a breast center by a breast cancer specialist to determine the appropriate treatment.

• Breast cancer survivors: A patient's breast cancer history and prior treatment may alter screening recommendations. For instance, individuals who have had a total mastectomy typically do not require screening imaging. However, patients with a history of mammographically occult cancer who have undergone a partial mastectomy may need MRI screening in addition to routine mammography. These patients should be evaluated by a breast cancer specialist at a dedicated breast center to determine the most appropriate screening strategy.

• High-risk patients: Individuals with a greater than 20% lifetime risk of developing breast cancer based on any risk assessment model, which considers factors such as family history, genetics, breast density, and personal history, are classified as high-risk. This group also includes those with biopsy-proven high-risk lesions. These patients should be evaluated at a dedicated breast center by a breast cancer specialist to determine the most appropriate screening approach.

Equipment

Breast Mammography

Mammography is a low-dose x-ray modality used for detailed imaging of the breast and is considered the most effective population-based screening method. This technique can detect microcalcifications smaller than 100 μm, allowing for the identification of lesions before they become palpable. Mammography is performed in 2 forms—screening and diagnostic.

A screening mammogram is the appropriate study for asymptomatic patients at average risk. A diagnostic mammogram is required for further evaluation if an abnormality is detected during screening.[12] Tomosynthesis and 3D mammography are preferred methods due to their enhanced ability to detect small cancers and reduce the likelihood of false positives.

Breast Imaging Reporting and Data Systems (BI-RADS) are used to guide breast cancer diagnostic evaluation. BI-RADS categorizes breast lesions in a standardized format, allowing for consistent interpretation among radiologists. However, most screening mammograms do not reveal evidence of cancer upon further testing. Approximately 1% to 2% of screening mammograms identify an abnormality that necessitates a biopsy, and around 80% of the biopsied lesions are benign.

Breast Imaging Reporting and Data Systems Scoring

BI-RADS stratifies imaging findings into the categories below and provides recommendations for further diagnostic evaluation based on these classifications.

• BI-RADS 0: Additional information is needed, and further imaging may be required. Prior mammograms may also be necessary for comparison. Specific recommendations for follow-up imaging should be outlined in the radiology report.
• BI-RADS 1: No abnormalities were detected on imaging. Routine screening should be continued.
• BI-RADS 2: Benign findings observed on imaging. Continued routine screening is recommended.
• BI-RADS 3: Findings are probably benign; the growth is unlikely to be cancerous but should be reimaged to confirm stability. A repeat mammogram is recommended within the next 6 months.
• BI-RADS 4: Findings are suspicious for cancer and may necessitate a biopsy. 
• BI-RADS 5: Imaging findings are highly suggestive of cancer; the growth is likely malignant and may require a biopsy.
• BI-RADS 6: Known biopsy-proven malignancy, cancer is confirmed, and treatment should begin immediately.[13]

Additional Breast Imaging Studies

MRI of the breast is generally more expensive than mammography, and it requires intravenous gadolinium contrast and takes longer to perform. However, MRI is more sensitive than mammography for detecting specific breast lesions and provides expanded views of the lymph nodes. In high-risk women, screening MRI is considered less specific but more sensitive than mammography for detecting invasive cancers.[5] Breast MRI is not recommended for women at average risk; however, it is advised for those with an elevated lifetime risk of breast cancer. This includes women with dense breast tissue, some patients with silicone breast implants, and individuals who cannot tolerate the discomfort caused by traditional mammography compression.

Thermography techniques measure elevated skin temperatures overlying breast cancers but are not routinely used in screening or included in standard screening guidelines.[14] Ultrasound is usually used to evaluate abnormalities detected during a clinical examination or screening mammography. This imaging modality can aid in assessing patients with dense breasts as an adjunct to screening mammograms. However, ultrasound has limited use as a primary screening technique due to various factors, including the inability to find microcalcifications and poor specificity.

Personnel

Patients may sometimes detect breast cancer by noticing changes in their breasts. They should be advised to inform their clinician of any changes occurring in their breasts. Any alteration in the breast should prompt a clinical assessment, with further diagnostic evaluation performed as indicated by current guidelines.

Primary clinicians should remain vigilant for patients at high risk for breast cancer, defined as having a greater than 20% lifetime risk according to any breast cancer risk assessment model (eg, Gail and Tyrer-Cuzick). For high-risk screening recommendations, these patients should be evaluated by a breast cancer specialist at a dedicated breast cancer center. Additionally, patients with a strong family history of cancers—particularly breast, ovarian, prostate, stomach, or pancreatic cancer—should be considered for genetic testing and referred to a genetic counselor if they express interest.

Preparation

Periodic assessment of the patient's personal and family history is essential for healthcare clinicians. This evaluation should include risk factors, prior biopsy results, radiation exposure, and family history of breast cancer. Identifying women who may benefit from genetic counseling and high-risk screening by a breast cancer specialist is crucial.[12] 

Recent studies promote the concept of breast self-awareness, which involves being attuned to the appearance and feel of a woman's breasts and the ability to notice any changes. Women are encouraged to report any changes to their primary healthcare clinician. In contrast, breast self-examination involves a regular and systematic approach to assessing the breasts.[15]

Technique or Treatment

Imaging techniques for breast cancer screening are most effective when considering both sensitivity and specificity while also accounting for potential complications and harms to the screening population. The preferred imaging method is mammography, followed by commonly used modalities such as ultrasonography and MRI. Additionally, breast self-examination and clinical breast examinations remain important components of breast cancer detection.

Screening methods, such as mammography, are most effective when targeted strategies are used, considering age and other factors, including hormonal exposure, family history, and risk factors such as radiation, obesity, and genetics. MRI involves the injection of intravenous contrast material, which enhances the ability to differentiate normal breast tissue from abnormal lesions.

Complications

Mammography has its limitations as a screening imaging method. Research indicates that it is less sensitive in detecting cancer in dense breast tissue, which can result in false-negative outcomes and the potential for missed cancers, if present. Some breast cancers may be mammographically occult, failing to appear on traditional mammograms. Thus, it is essential to conduct imaging alongside a physical examination by a healthcare clinician. Further diagnostic imaging, such as MRI or ultrasound, should be ordered when discrepancies arise. Additionally, high-risk patients should be screened appropriately, often utilizing MRI for more accurate detection.

Increased treatment interventions are associated with screening, which may not always be effective or necessary. Individuals who undergo screening are more likely to experience surgery and radiation therapy. Overscreening can have negative consequences for patients, including economic, psychological, cosmetic, physical, and productivity-related harm. The overall lifetime radiation exposure increases with the age of initiation, frequency, and cessation of screening, as women are exposed to approximately 3.7 mGy per digital mammogram. This raises the risk of radiation-induced breast cancer to 125 cases per 100,000 women aged 40 to 74, potentially leading to an increase in deaths attributed to breast cancer screening.

Ultrasonography is generally considered a highly operator-dependent modality and supplemental screening test that requires a skilled practitioner, high-quality examination, and state-of-the-art equipment. Based on the findings from various studies, a prospective, multicenter study is warranted to further investigate the role of this imaging modality in breast cancer screening.[16]

Clinical Significance

Age should not be the sole factor in determining breast cancer screening. A comprehensive assessment of all relevant risk factors—including breast density, genetics, and personal history—should guide the screening process.[17] Additionally, the sensitivity and specificity of mammography tend to improve with advancing age compared to younger women.

Dense breast tissue is a common finding on mammograms, particularly in younger women, as breast density typically decreases with age. However, dense breasts, especially in older patients, are associated with a higher likelihood of developing breast cancer, and small lesions can be more challenging to detect on traditional mammograms. While mammography may reduce sensitivity in detecting breast cancer among women with dense breasts, alternative screening strategies such as MRI and ultrasonography can be utilized. These methods are particularly recommended for women at higher risk of developing breast cancer.

An early age of initiation for screening and the use of MRI and ultrasound may be considered for women with first-degree relatives diagnosed with breast cancer.[5] For BRCA mutation carriers, a combination of annual breast MRI and mammography is recommended for breast cancer screening. It is essential to accurately identify patients with a greater than 20% lifetime risk of breast cancer and to recognize that standard screening guidelines for asymptomatic average-risk patients do not apply to this population. High-risk individuals should be referred to a breast cancer specialist for tailored screening recommendations and, if appropriate, to a genetic counselor for genetic testing.

Enhancing Healthcare Team Outcomes

Screening average-risk breast cancer patients necessitates a collaborative and interprofessional approach to enhance patient-centered care, improve outcomes, and ensure safety. Physicians, advanced practitioners, nurses, pharmacists, radiologists, and technicians must work together to balance the benefits and risks of screening. Clinicians are responsible for identifying risk factors and providing appropriate screening based on age, breast density, and family history. Effective counseling, especially for patients with genetic predispositions, requires shared decision-making. Radiologists and technicians must skillfully perform and interpret imaging to minimize false positives and negatives. This coordinated effort fosters a comprehensive care strategy that improves diagnosis and patient outcomes.