Continuing Education Activity

With improved screening and diagnostic techniques, the incidence and prevalence of breast cancer are rising worldwide. In 2018 alone, there were 2.2 million cases of breast cancer diagnosed worldwide, and most were discovered by imaging. However, there are limitations to breast imaging evaluation. The majority of suspicious breast lesions require further diagnostic workup with a biopsy and pathological diagnosis to determine management. This activity describes how to perform an ultrasound, mammographic stereotactic, and magnetic resonance (MR) guided breast biopsy and explains the role of the machines, procedural team, and techniques used in evaluating and managing suspicious breast masses in patients who undergo imaging-guided biopsies.

Objectives:

• Describe the anatomical structures of the breast and the embryologic origin of breast parenchyma.
• Review the equipment, personnel, preparation, and technique required to perform a breast biopsy.
• Identify the potential complications and clinical significance of a breast biopsy.
• Outline interprofessional team strategies for improving care coordination and communication to advance breast biopsy procedures and improve patient outcomes.

Introduction

Breast cancer carries a high cost to society; the loss of life and the economic impact is almost unimaginable. In 2018 alone, there were 2.2 million cases of breast cancer diagnosed worldwide, and most were discovered by imaging.[1] However, there are limitations to breast imaging evaluation.

The majority of suspicious breast lesions require further diagnostic workup with a biopsy and pathology diagnosis to determine management. Historically, a surgical excisional biopsy was the only option and was only feasible for masses large enough to be localized by palpation intraoperatively.

In the mid to late 1980s, a series of practical breakthroughs occurred to propel minimally invasive procedures into a new age. Initially, when the minimally invasive ultrasound-guided biopsy was developed, it required three hands - one hand to operate the ultrasound probe and two hands to operate the biopsy needle. Lindgreen, a radiologist, frustrated with the clumsy nature of this method, developed a biopsy device that could be used with one hand by a system of springs and buttons. This allowed an individual provider to control the ultrasound transducer with one hand and the biopsy device with the other.

The second breakthrough was the modification of the mammographic controlled stereotactic system primarily used for fine needle aspirations to accept the modified biopsy device.[2] The third breakthrough occurred with the integration of magnetic resonance (MR) guidance and the modification in the previously developed biopsy devices to be MR compatible. Today, millions of breast biopsies are performed annually using these minimally invasive techniques as a cost-effective alternative to surgical excisional biopsies with high accuracy and low complication rates.[3][4]

Anatomy and Physiology

The breasts develop from the embryologic mammary ridges/milk lines, which extend from the axilla to the groin. During fetal development, the caudal portions of the milk lines regress with the persistence of the cranial portions, which overlie the pectoralis muscle groups. The nipple-areolar complex begins to form around the 12 weeks of gestational age when mesenchymal cells differentiate into smooth muscles and form Montgomery glands and the mammary ducts. Breast development becomes quiescent until puberty when the breast mound and areola increase in size in response to sex hormones.[5][6]

The skin overlying the breast is made up of avascular epidermis and the dermis, which contains dermal appendages - sebaceous glands, sweat glands, hair follicles, as well as small blood vessels, lymphatic channels, and nerve endings. Below the dermis, the hypodermal layer contains larger blood vessels, lymphatic channels, nerve cells, and adipose tissue.[7] This is followed by a thin fascial layer that separates the breast parenchyma from adjacent structures. This fascial layer is anchored to the skin via suspensory ligaments, also known as Cooper ligaments. The Cooper ligaments, in combination with subcutaneous fat and glandular tissue, are ultimately responsible for the breast shape.[8]

The breast parenchyma is a collection of sac-like dilations known as ductules or acini that are lined by the specialized cuboidal cell that produces milk in response to hormonal control. Collection of ductules are known as a lobule; ductules within a single lobule communicate with each other via the intralobular terminal duct. The intralobular terminal duct communicates with an extralobular duct, and together the lobule and extralobular duct are termed the terminal ductal lobular unit (TDLU). The TDLU is generally the smallest functional unit discussed in breast imaging and is the primary site of breast cancer. Multiple TDLU coalesce to form a breast lobe. There are approximately 12-20 breast lobes per female breast. These lobes are identified by a single main draining duct that communicates with the nipple-areolar complex. Prior to communicating with the nipple-areolar complex, the main duct focally dilates to form the lactiferous sinus, the site where breast milk is stored.[8]

Blood supply to the breast is provided via perforating arteries from the internal mammary arteries, intercostal perforators, and branches of the axillary artery. The venous draining of the breast is variable. Generally, deeper draining veins accompany the deeper arteries while the superficial venous drainage is variable. The lymphatic drainage is primarily to the ipsilateral axilla and less so to the internal mammary /infra-clavicular system. 

The lymphatic drainage is very important from a breast imaging standpoint, and evaluation of the ipsilateral axilla should be performed on any exam with findings that are suspicious for breast cancer. Anatomically, the axilla is triangular to pyramidal shaped space adjacent to the thorax and upper extremity. The margins of the axilla are loosely defined as the lateral wall of the chest, medial wall of the humerus, one rib, and scapula. This space primarily serves as a conduit for traversing neurovascular and lymphatic structures of the chest with the upper extremity.[9]

Indications

The Breast Imaging and Reporting System (BIRADS) published by the American College of Radiology (ACR), provides a classification system for breast masses and biopsy criteria. The classification system is based on imaging features correlating to cancer risk, and range from 1 through 6, the greater the classification, the higher likelihood of cancer. Generally, a breast biopsy is indicated in any patient with a complex cyst, solid mass, indeterminate or suspicious solid mass, indeterminate or suspicious microcalcifications, and suspicious architectural distortion.

Contraindications

An absolute contraindication for an image-guided breast biopsy is the non-visualization of the lesion. Relative contraindications are overlying skin infections and a high risk of bleeding demonstrated by a grossly abnormal international normalized ratio (INR). For a stereotactic biopsy, morbid obesity is a relative contraindication as biopsy chairs and tables have a weight limit, usually only accommodating patients up to 350 lbs. Additionally, modality-specific contraindications for mammographic stereotactic guided biopsies include pregnancy (relative), breast compression size, and inability to properly position the patient. These same contraindications hold true for MR with the addition of MR noncompatible implanted hardware or metallic devices.[10][11]

Equipment

Imaging Equipment: American College of Radiology (ACR) and the United States government provide specific guidance and accreditation standards for a breast ultrasound (US), mammographic, and MR machines. Most of these standards are a part of an institution’s quality control program performed at regular intervals by certified medical physicists or associates. It is imperative that institutions obtain and maintain accreditation standards when performing breast imaging and interventions.  US machines come in a variety of configurations and capabilities; this article will focus on hand-held US machines utilized in brightness mode. These machines are generally equipped with interchangeable hand-held transducer (probe), and a display/monitor, which vary per manufacturer. The machines produce images by intermittently transmitting ultrasonic waves through the probe and into a thin slice of the body. Then the machine measures returning frequencies, amplitude, and time-to-return. A series of mathematical calculations are performed and displayed as different levels of brightness on the monitor. Usually in the form of an image.[12] The tissue composition combined with the physical properties of the probe and technical factors greatly affect the image quality.

The mammographic guided stereotactic biopsy machine is a specialized device that develops images using ionizing radiation. Generally, these devices are similar to mammographic machines used in women’s imaging with roughly three types being mass-produced:

• Specially designed machines for biopsies only
• Mammographic units with add on biopsy devices
• L-arm type mammographic devices

These devices are produced by a number of manufactures with some differences in biopsy table/chair apparatus and software capabilities. Patient positioning varies per machine. Options include prone, sitting, and lateral decubitus.[13] Newer machines also offer the ability to perform tomosynthesis (3D mammogram) guided biopsy.

MR imaging uses a combination of radio frequencies and magnetic field strength to produce images. Simplistically, a supercooled electromagnet produces a magnetic field, which the patient is brought into. The magnetic field is then altered by the use of coils, the patient, and radio frequencies. The subsequent change/alterations are measured and used to produce an image.[14] The remaining physics behind MR is beyond the scope of this paper. MR biopsy protocols change from institution-to-institution and between scanner types. It is important to remember that while MR does not use ionizing radiation, there is a risk associated with this modality primarily related to the magnetic field and its interactions with ferrous metal components such as implanted cardiac devices and neurostimulators. Newer imaging-guided techniques centered on nuclear medicine through the use of gamma imaging and positron emission mammography show promise. However, these imaging modalities are not commonly used, and further discussion is beyond the scope of this paper.[15][16]

Tissue Sampling Devices: Fine Needle Aspiration (FNA) is a familiar procedure for most physicians and can be performed under the US, mammographic, or MR-guidance. Typically, a 21 gauge to 27 gauge beveled needle of variable length is placed into the target lesion in a to-and-fro motion. The needle can be attached to a small syringe (2 mL to 20 mL). If the needle is attached to a syringe, slight negative pressure is applied to the syringe to assist in sample collection. This technique requires the aspirate sample to be placed on a slide and immediately evaluated by cytopathologic or tech for sample adequacy. The advantage of this device is the ease of use, while the disadvantages are the volume of tissue, lack of histopathologic data, and sensitivity. This device has a limited role in breast cancer diagnostic workup and is largely replaced by the core needle biopsy device.[17]

Vacuum-assisted biopsy devices (VAD) are made by a number of manufacturers but have basic similarities. These similarities include a core needle-type system ranging from 9 gauge to 14 gauge, between 9 cm to 12 cm in length, with terminal biopsy aperture 12 mm to 20 mm in length. Multiple vacuum holes on the opposite side of the aperture, which assist in sampling, and a thin hollow cutter type blade/cannula that slides over the aperture during sampling. Some systems have a rotating knob, which allows the aperture to spin while the housing remains stationary, while other systems require the user to rotate the housing during the procedure if sampling is desired at different angles. During the sampling phase, a vacuum pulls tissue into the aperture under negative pressure. The tissue is then cut from the breast by the cannula as it passes over the aperture and seals the device. It is imperative to assess adequate vacuum pressure of 25 mmHg to 35 mmHg throughout the procedure if the vacuum pressure is less than this the tissue samples may be inadequate.[18][19] Immediately after sampling, a small amount of sterile saline and anesthetic is infused through the device to numb adjacent tissue. At the same time, the infused fluid and negative pressure pull the sample into a collection reservoir and can be emptied as needed throughout the procedure. This process is repeated until adequate sampling is achieved. Additionally, this device is compatible using the three previously mentioned imaging modalities. The benefits of a VAD include the ability to sample a cystic-solid mass and to obtain multiple samples without removing the biopsy device. The disadvantages include difficulties associated with performing multiple biopsies within the same breast.

Spring-loaded core needle biopsy devices are common throughout the procedural rooms of hospitals and outpatient clinics. These devices typically come in sizes similar to the VAD, but with wider variation in needle sizes and gauges. Spring-loaded biopsy devices are similar to a stylet with an aperture at the distal end. The stylet is propelled forward from potential energy stored within the corresponding spring, called a throw. The throw can be adjusted on some models from 0.5 cm to 2.5 cm, depending on the manufacturer. Similar to the VAD, a cutting cannula is then deployed over the aperture, and a sample is taken. The device is removed, and tissue samples are collected after re-exposing the aperture and rolling the device onto a sterile gauze or into a tissue cup. This process can be repeated as needed.[20] Most kits come with a larger introducer needle that can remain in the patient in between tissue sampling to assist in target lesion localization. The benefits of this type of device are cost-effectiveness, simplicity, and ability to perform multiple biopsies of separate lesions within the same breast quadrant quickly.[21] The drawbacks to this device include trauma associated with repeat removal and re-introduction, as well as the complications associated with air entering the imaging field.

Personnel

The Mammography Quality Standards Act (MQSA) publishes specific requirements for breast biopsies and accreditations. To summarise, a breast biopsy should be performed by a physician who understands the technology in the machine, physics used to produce an image, limitations of the technology as well as common artifacts associated with breast imaging. Additionally, physicians and technicians must demonstrate knowledge of breast anatomy, and be able to recognize physiologic breast changes and common breast pathologies.[22] 

Preparation

Before any biopsy, the patient’s previous imaging should be reviewed. At that time, a tentative plan is developed with an emphasis on patient positioning, the shortest distance from skin to the lesion, and the identification of important structures such as blood vessels and breast implants. Traditionally US-guided breast biopsies are performed with the patient lying supine to slightly anterior oblique on an examination table. To reduce shifting of tissue due to gravity, the side to be evaluated is elevated, and the ipsilateral arm flexed over or under the head (right breast right side is anterior oblique, and the right arm is positioned over the head).[23] Both mammographic stereotactic and MR-guided biopsies can be performed with the patient in a comfortable seated position, semi-prone, or prone position via biopsy chair or table. An important note is that the majority of MR-guided biopsies are performed with the patient in the prone position. The affected breast is placed between a compression plate and backplate with subsequent mild compressive force applied to immobilize the breast throughout the procedure.[13][23] In all scenarios, care must be taken to respect the patient’s modesty and privacy.

Technique

US-Guided Technique: When performing an ultrasound-guided biopsy, the transducer should be broad bandwidth, high frequency, and linear array. The transducer’s focal zones and the machine’s power, gain, and time-gain constant should be optimized.[24][25] Advanced US imaging, spatial compounding, harmonic imaging, extended field of view, elastography, 3D, and speckle reductio are commonly used, but further discussion is beyond the scope of this paper. After ensuring adequate quality control and identification of the target lesion, the overlying skin is anesthetized, followed by the deeper tissue along the expected biopsy trajectory.

Depending on the size and type of biopsy performed (spring-loaded or VAD), a dermatome might be required. While maintaining appropriate transducer pressure and visualization of the target lesion, the needle is advanced into the breast. It is imperative the operator maintain constant visualization of the needle tip to ensure adjacent structures are not damaged, and the trajectory of the needle is parallel to the underlying chest wall. This will help limit the complications discussed later in this paper. This technique is real-time; the biopsy apertures should be visualized within the target lesion and image saved for post-biopsy review. Generally, 4 to 10 samples are taken to assist in tissue diagnosis. After completion of the biopsy, removal of the device, and placement of a biopsy marker, manual pressure should be applied to mitigate the possibility of developing a hematoma. A post-biopsy mammogram is subsequently obtained and compared to pre-biopsy imaging to confirm the on-target biopsy and appropriate biopsy marker placement.[24][26] This is extremely important in cases where the imaging and tissue diagnosis are discordant. The advantages of this technique are faster procedural time, real-time visualization of accuracy, lack of ionizing radiation, and increased patient comfort secondary to lack of breast compression.[26]

Mammographic-Guided Technique: During a mammographic stereotactic guided biopsy, the breast is placed between a compression plate and imaging receptor. Then an X-ray type image is obtained at 0 degrees (scout image). If the lesion is seen within this image, subsequent off-angle images are obtained at roughly 15-degrees and -15-degrees relative to the 0-degree position (the scout image plane). Using proprietary software, the machine provides a coordinate set relative to a known reference point (this is different on different machines).[13] 

Once adequate imaging is obtained, the breast is prepped and draped in a sterile fashion. The skin overlying the entrance point is locally anesthetized, followed by placement of anesthetic into the subdermal tissue and breast parenchyma within the expected biopsy needle track. At this time, some institutions repeat the scout images to ensure that the lesion has not moved. After confirmation of the lesion’s location, a dermotomy is performed at the expected skin entrance point prior to the advancement of the biopsy needle. The needle is then advanced through the dermotomy to the desired depth via the coordinate system. The second set of 15-degree and 15-degree images is then obtained to confirm accurate needle positioning. Tissue sampling is performed with a VAD along multiple axes. Usually, 6 to 12 samples are obtained. After sampling but prior to the removal of the biopsy device, the tissue samples are evaluated under x-ray to ensure the target lesion was sampled. Target lesions are typically indicated by the presence of the same suspicious calcifications seen on diagnostic mammograms.

Once adequate sampling has been confirmed, the biopsy device is removed, and a subsequent biopsy marker is placed. The patient is then brought out of compression, and manual pressure is provided to the biopsy site. A post-biopsy mammogram is obtained and compared to pre-biopsy imaging to ensure appropriate sampling and biopsy marker placement.[18][23] A mammographic stereotactic biopsy via the spring-loaded device is performed similarly to the VAD technique, with the exception that the samples are collected after each biopsy throw. The advantage of this technique is the ability to target mammographically suspicious, but ultrasound occult lesions such as suspicious microcalcifications. The disadvantages include cost adversity, time of the procedure (greater than ultrasound), and exposure to ionizing radiation.

Magnetic Resonance-Guided Technique: These breast biopsies are generally performed on a 1.5T or 3T machine with the patient in the prone position. The breast is placed in compression and prepped in a similar process as a mammographic stereotactic biopsy. The biopsy is generally attempted from the lateral to the medial aspect of the breast. Imaging guidance is provided using a basic grid type system, post, and pillar, as well as freehand. Commonly a sagittal T1 fat saturation pre and post-contrast sequences are obtained. The needle is then advanced (sagittal plane) under intermittent imaging guidance. This process is repeated until adequate positioning is achieved. Then, as in mammographic stereotactic biopsies, a VAD or spring-loaded device is used with 6 to 12 samples obtained. The needle is removed, and a biopsy marker is placed, followed by manual pressure. Most institutions obtain a post-biopsy mammogram to confirm biopsy marker placement.[27][28] This technique is beneficial in that it allows a targeted biopsy of mammographically and ultrasound occult lesions and lacks the ionizing radiation exposure of mammographic guidance. However, it is also the most cost adverse and time-consuming with variable specificity correlated to clinical presentation.[27] Additionally, there is a theoretical risk associated with gadolinium exposure.

Complications

Minimally invasive breast biopsies are generally well tolerated. However, skin bruising, hematoma, and biopsy marker migration are the most common complications that occur. Whereas implant ruptures are less frequently reported.[18][19][27] The rarest and severe complications are hemothorax, pneumothorax, and hemopneumothorax, with case reports present in the literature.[29] These rare complications can generally be avoided with the appropriate technique. All breast biopsy patients should be briefly monitored for complications.

Clinical Significance

Ultimately, the clinical significance is dependent on patients' age, risk factors, and location of pathology. Should pathology involve the breast parenchyma, there is an expected increase in patient morbidity when compared to pathology involving the skin, dermal appendages, or adjacent musculoskeletal structures. This is why, after every biopsy, the patient's pertinent imaging is reviewed to include the biopsy and samples in conjunction with the pathologic report. In the event that the imaging features and the pathologic report are discordant further diagnostic workup is needed, usually in the form of repeated minimally invasive biopsy or surgical excisional biopsy.

Enhancing Healthcare Team Outcomes

Breast cancer is the most common cancer affecting women worldwide. Breast cancer care/management has increased in complexity throughout the years, with an interprofessional approach adopted by the majority, if not all, institutions. A breast cancer team is usually comprised of multiple disciplines: physicians, surgeons, breast cancer nurses, (occasionally) medical physicists, psychiatrists, and technicians. In literature, this interprofessional approach has demonstrated decreased mortality.[30] [Level 4] American Joint Commission on Cancer (AJCC) accepted the TNM staging manual requires not only information regarding tumor size, lymph node involvement, and metastasis, it includes hormone receptor status, histologic grade, proliferation markers such as Ki-67, biologic markers and genomic profile as prognostic factors.[31] The aggregation of this data across multiple centers has led to the advent of precision medicine with efforts to personalize treatment.[32] [Level 4] Even after the successful treatment of breast cancer, women with a personal history of breast cancer remain at an elevated risk for the development of new breast cancer compared to baseline screened population. This knowledge is essential for primary care physicians and breast cancer nurses to ensure adequate surveillance imaging with advanced imaging techniques if indicated.[33] [Level 4] Given the complexity of the team, the breast cancer nurse plays a pivotal role in facilitating care with numerous providers and ensuring a correct follow up with appropriate studies.[34] [Level 5] Altogether, the interprofessional team approach is believed to help decrease morbidity and possible mortality from breast cancer through access to care, planning, and interprofessional communication.[35] [Level 5]