Continuing Education Activity

In women, breast cancer is number one in incidence and mortality when compared to all cancers. It is the most common non-skin cancer and second deadliest cancer in women than for any other cancer. This activity describes different aspects of breast cancer screening, which is the most common cancer in women worldwide and is also the second commonest cause of cancer mortality in women in the United States. It also highlights the role of new diagnostic radiology practices and the interprofessional team in the detection of breast cancer.

Objectives:

• Describe the breast cancer screening guidelines as advocated by the American Cancer Society, United States Preventive Services Task Force, World Health Organization, American College of Obstetricians and Gynecologists, and National Comprehensive Cancer Network.

• Review the most commonly used techniques to screen breast cancer.

• Outline the potential complications of breast cancer screening such as false-positive tests, possibilities of over-diagnosis, radiation hazards, and patient discomfort.

• As the number of breast cancer cases are increased with the widespread use and implementation of breast cancer screening methods, the complications and harms done due to overtly applying screening strategy may lead to harm more than benefit. Thus, a balance has to be achieved, and for this, it is crucial to maintain coordination among the interprofessional team to ensure the best patient outcomes.

Introduction

In women, breast cancer is number one in incidence and mortality when compared to all cancers.[1] It is the most common non-skin cancer and second deadliest cancer in women. In theory, diagnosing early-stage tumors should reduce mortality; however, it is critical to incorporate lead-time bias. The issue of concern is to determine who should be screened. There could be some slow-growing tumors that do not become clinically evident during the patient's life. Therefore, risk stratification, the age to begin screening, and the age to stop screening are critical for the appropriate screening of breast cancer. More recently, rather than focusing on the size and extent of a tumor to guide therapy, the focus has been on determining biological characteristics that can help guide the prognosis and plan.[2]

The methods of screening are:

• Breast palpation may be done by clinical breast examination and breast self-examination.
• Breast imaging techniques such as mammography, ultrasonography, magnetic resonance imaging (MRI), and digital breast tomosynthesis (DBT)

Many multiple randomized trials have come to the consensus that routine screening mammography should be offered to women ages 50 to 69 rather than that for women of the age group 40 to 49 or women over 70 years of age. Genetic mutations have been discovered, and an increase in the risk of breast cancer and the development of breast cancer risk prediction models have stimulated rigorous efforts to develop screening methods for risk stratification. For high-risk women, in addition to mammography, ultrasonography & breast magnetic resonance imaging (MRI) have been studied as screening methods.[3] The discussion will include patient risk stratification and management options for women with a genetic predisposition to breast cancer. Surveillance in women with a personal history of breast cancer is discussed in detail separately.

Anatomy and Physiology

The mature adult breast comprises skin, subcutaneous tissue, epithelial, and stromal components. The epithelial component is comprised of branching ducts that connect the structural and functional units of breasts, known as lobules to the nipple. The stromal component comprises the majority of the breast volume in a non-lactating breast and is composed of fibrous and adipose tissue. The breast tissue extends from the 2 and 6 ribs vertically and sternal edge to midaxillary line horizontally. A part of breast tissue projects into the axilla and is known as the axillary tail of Spence. The skin of the breast is thin and contains sebaceous glands, exocrine sweat glands, and hair follicles. The nipple is devoid of hair follicles and contains abundant sensory nerve endings and sebaceous and apocrine glands. The areola, which measures about 16 to 60 mm, is nearly circular and has higher pigmentation. There are elevations near the periphery of the areola, which form due to the opening of ducts of Montgomery glands, which are large sebaceous glands and are known as Morgagni tubercles. The Montgomery glands represent a stage between sweat and mammary glands. The breast is covered with the superficial pectoral fascia, which continues with the superficial abdominal fascia of Camper. The breast is covered from the underside with deep pectoral fascia, which covers the muscles pectoralis major and serratus anterior. The two fascial layers covering the breast tissue are connected by fibrous bands known as Cooper suspensory ligaments that provide natural support to the breasts. The majority of total breast blood supply comes from internal mammary vessels. Sensory innervations are mainly from anterolateral and anteromedial branches of thoracic intercostal nerves T3 to T5. It is also supplied by lower fibers from supraclavicular nerves of the cervical plexus.

Indications

In 2015, the American Cancer Society (ACS) recommended that

• Women with an average risk should undergo regular screening mammography starting at age 45 (strong recommendation).
• Women who are between 45 to 54 years should undergo screening annually, and women 55 years and older can undergo biennial or annual screening.[4]
• It recommends that women aged 40 to 44 are to be given a choice to start annual mammography.
• Routine screening strategies are not strongly advised for women in age groups of 40 to 49 or those above the age of 70.[5] However, in collaboration with mammography, breast MRI has been studied as an important screening method for high-risk females and those with dense breasts.[3] Women are advised to continue screening mammography who have until ten years of life expectancy and good health in general.

The United States Preventive Services Task Force (USPSTF)

It recommends biennial mammography in women of age group 50 to 74. For the age group 40 to 49, group screening can be considered after discussing and evaluating the risks and benefits of this test with their physician.[6]

WHO

It advises biennial mammography screening for women aged 50 to 69 years in well-resourced settings.

American College of Obstetricians and Gynecologists

It recommends twice-annual screening mammography after 55 years of age, which prevents harm as long as the patient is informed.

The USPSTF and ACS differ markedly in terms of recommendations for clinical breast examinations (CBE). ACS does not recommend them, while the USPSTF recommends a clinical breast examination with mammography in women with an average risk of developing breast cancer.

The panel of the National Comprehensive Cancer Network (NCCN) recommends women with average risk in the age group of 25 to 39 years to have a clinical assessment, risk reduction counseling & clinical breast examination every 1 to 3 years. They should also be recommended to inform about any changes in their breast to their health care provider immediately.[6]

Contraindications

Certain precautions are to be taken for breast screening considering the age of a woman. New guidelines by the American College of Physicians suggest that it is cautioned that beginning at the age of 40, average-risk women with no symptoms should discuss with their physician regarding benefits, personal preferences, and potential harms of breast cancer screening with mammography before the age of 50. 

Clinical breast examinations screening is not recommended no matter what age for average-risk women. The screening for those aged 75 years or older or with a life expectancy of 10 years or less should stop.[5]

Equipment

Mammography is a low-dose x-ray modality for detailed imaging of the breast. It is the best population-based method for screening. It can demonstrate micro-calcifications less the 100 micrometers, which makes it capable of detecting lesions before they become palpable. Mammography can be done in two forms, screening and diagnostic. Those with a family or personal history of breast cancer require additional views in diagnostic/screening mammography.[7]

Breast imaging reporting and data systems are used to guide the breast cancer diagnostic rule. It involves levels of categorization to interpret breast lesions in a standardized format among radiologists. However, the majority of screening mammograms show the absence of evidence of cancer on subsequent testing, 1% to 2% show abnormality requiring biopsy. The majority (80%) of these are benign lesions.

BI-RADS scoring:[8]

• 0—Need more information. Another mammogram may be needed.
• 1—No abnormality. Continue routine screening.
• 2—Benign breast conditions, such as cysts. Continue with routine screening.
• 3—Something which is probably not cancer is detected. A repeat mammogram within the next six months.
• 4—Suspicious of cancer. May need a biopsy.
• 5—Highly suggestive of cancer. It will need a biopsy. 

Digital mammography can be applied better to diagnose breast cancer in dense breasts. Tomosynthesis or 3D mammography may also be used, which improves the ability to find minutely sized cancers and decrease the probability of false positives.

Magnetic resonance imaging (MRI) cost is higher than for mammography worldwide. 

Thermography use is based on the fact of elevated breast skin temperatures overlying breast cancers.[9]

Ultrasound is usually used to know more about the positive clinical examination or screening mammography on diagnostic fronts. It has limited use as a screening device due to various factors, including the inability to find micro-calcification and poor specificity.

Screening MRI is considered less specific, but more sensitive than mammography in high-risk women for detection of invasive cancers.[3]

Annual mammography and MRI, and at times at 6 months duration, is needed for women with BRCA gene mutations, strong family history of breast cancer, and prior chest radiation therapy.

Personnel

As a patient can herself find breast cancer at times, she should not only be informed and made aware of the breast self-awareness but also instructed to notify the health care provider if and when any change in the breast occurs.The health care providers should be affluent with screening and counseling asymptomatic patients with a family history of BRCA cancers. Genetic counselors and the team should be doing assessments to provide genetic testing after informed consent.

Preparation

Patients’ history – personal as well as family is important to be assessed periodically by the health care providers. This should include risk factors, prior biopsies, and their results, radiation exposure, as well as a family history of breast cancer. The identification of women who will benefit from genetic counseling is essential. The Gail model is used to assess and stratify high-risk women.[7] 

Breast self-awareness is promoted according to new studies. Breast self-awareness is guided by the appearance and feel of the woman’s breasts and the ability to notice any change in the breasts and report to the primary health care provider; however, in breast self-examination a regular and systematic way to examine breasts as in self-examination.[10]

Technique or Treatment

Imaging techniques for breast cancer screening are best and well accepted from a sensitivity and specificity point of view, keeping into consideration the complications and harms to the screening population. Others are breast self-examination and clinical breast examination. Amongst the imaging techniques, mammography is best accepted. Other commonly used ones are ultrasonography and MRI.

Screening methods like mammography are most effective when targeted screening strategies are used, keeping age into considerations and other criteria like hormonal exposure, family history, and risk factors like radiation, obesity, and genetics.

Magnetic resonance imaging (MRI) is done by injection of intravenous contrast material, which increases the ability to delineate the normal breast from abnormal lesions.

Complications

The mammography screening method is not accurate. Data suggests that it can be less sensitive in detecting cancer in mammographically dense breast tissue. Mammography may lead to false-negative results leading to missing cancer when it is present.

Additional treatment is associated with screening, which may not be effective and needed. Those who are screened are more likely to have surgical and radiation therapy.

And the treatment may harm economically, psychologically, physically, or productively. There has been uncertainty in estimating expectancy of life along with decreased quality-adjusted life expectancy due to overdiagnosis. 

Depending on the age of initiation, frequency, and cessation of screening, the overall lifetime radiation exposure increases as women have exposure of about 3.7 mGy per digital mammography. They are hence increasing radiation-induced breast cancer risk of 125 cases per 100,000 women in those aged 40 to 74 years. And thus, an increased number of deaths due to breast cancer screen.

Ultrasonography is generally considered to be a highly operator-dependent modality and supplemental screening test that requires a skilled practitioner, high-quality examination, and state-of-the-art equipment. Given the results of these studies, a prospective, multicenter study is warranted to examine the role of this modality of imaging in breast cancer screening.[11]

Clinical Significance

Age should not be the only deciding factor to discontinue or continue breast cancer screening. Combinations and a balanced overview of all risk factors and density of breasts should be considered while planning for breast screening age-wise.[12] The sensitivity and specificity of mammography become higher as age advances in comparison to young aged women. 

A dense breast has a high probability of developing breast cancer. While mammography decreases the sensitivity of detecting breast cancer in women with dense breasts, other screening strategies like MRI and ultrasonography may be employed.

It has been observed that women have fast-growing breast cancers, and mammography cannot be of much help here from a screening perspective. It is advisable to discuss breast cancer screening with all women from age 40, and proper documentation should be done.[6] According to the new guidelines, age alone should not be the guiding factor to stop screening. Women having an average risk of breast cancer should continue breast screening mammography until at least 75 years of age. General health and life expectancy should be considered.

Early age of initiation and use of MRI and/or ultrasound, may be considered for women with the first-degree relative with breast cancer.[3] A combination of annual breast MRI plus mammography for breast cancer is recommended in women who are BRCA mutation carriers.

Enhancing Healthcare Team Outcomes

The screening of breast cancer is a challenging and complex arena of clinical care as well as preventive health care. The domain of primary health care is not only for appropriate screening and apt history, but also abilities to know and find the inherent risk factors which may cause an imbalance in the benefit obtained from screening. Keeping the age and density of breasts into consideration, proper counseling for genetic and familially predisposed patients, a shared opinion approach has to be sought.[7] 

From the diagnostic fronts, the knowledge, skills, and abilities of radiologists, as well as technicians and nursing staff, are recommended to support and obtain required details to add to the process of screening, decreasing the probabilities of false positives as well as false negatives.[3]

The coordinated and cooperative approach of the interprofessional team will increase the probability of diagnosis by the screening methods and enrich the health care support to the patients.