Continuing Education Activity

Globally, over 2 million new cases of breast cancer were diagnosed in women in 2020, and breast cancer remains the second most common cause of cancer-related deaths. In the United States, breast cancer accounts for 30% of new yearly cancer diagnoses in women. However, the mortality from breast cancer has been declining due to improved detection and advanced treatments. Vigorous screening and sophisticated diagnostic techniques increase the detection of occult breast cancer. This activity delves into the current standards of image-guided biopsies, emphasizing ultrasound, mammography, and magnetic resonance techniques. The advantages and disadvantages of the procedure are highlighted.

This course empowers clinicians to enhance diagnostic accuracy and improve the management of breast cancer by elucidating the interplay between imaging equipment, tissue sampling devices, and biopsy guidance modalities. Participants will gain proficiency in applying various tissue sampling devices, including fine needle aspiration, vacuum-assisted biopsy, and spring-loaded core needle biopsy devices. Interprofessional collaboration among primary care clinicians and treating surgeons is emphasized for positive postoperative outcomes.

Objectives:

• Apply knowledge of fine-needle aspiration, vacuum-assisted core biopsy, and spring-loaded core needle biopsy devices to select the best approach based on clinical presentation.

• Differentiate between biopsy techniques, including ultrasound-guided, mammography-guided, and magnetic resonance-guided approaches.

• Identify appropriate candidates for stereotactic and needle breast biopsies based on clinical indications.

• Collaborate with interdisciplinary teams for comprehensive cancer care in testing patients with stereotactic and needle breast biopsy.

Introduction

Breast cancer remains the second most common cause of cancer death among women worldwide. In 2018, 234,087 cases were diagnosed in the United States, and 2.2 million were diagnosed globally.[1] Most of the asymptomatic and nonpalpable cancers are diagnosed by screening mammograms or other imaging modalities.[2] An increase in the incidence of breast cancer is found in women younger than age 50, and these cases are often histologically unfavorable.

A tissue diagnosis of any breast lesion is necessary to determine the appropriate treatment. Historically, the only diagnostic option was an excisional biopsy, reserved for palpable masses. Diagnosing breast lesions visible only on mammograms presented a significant challenge; initially, lesions were tagged for biopsy using a wire, dye, or carbon.

Dr. Steve H Parker's stereotactic core biopsy in the late 1980s marked a revolutionary shift in how women with mammography-detected lesions are biopsied and treated.[3] Many subsequent advances, such as incorporating the biopsy needle into the mammographic stereotactic system and improving the magnetic resonance imaging (MRI) compatibility of the biopsy device, have resulted in millions of breast biopsies performed annually with high accuracy and low complication rates, providing a cost-effective means of yielding histologic information for patients with nonpalpable breast cancer and an alternative to surgical excisional biopsies.[4][5]

Anatomy and Physiology

The breasts form from the mammary ridges during embryonic development. Breast development slows until puberty, when the breast mound and areola grow in response to sex hormones.[6][7] The skin overlying the breast comprises the avascular epidermis and the dermis, which contains dermal appendages, such as sebaceous glands, sweat glands, hair follicles, small blood vessels, lymphatic channels, and nerve endings. The hypodermal layer contains larger blood vessels, lymphatic channels, nerve cells, and adipose tissue, followed by a thin fascial layer that separates the breast from adjacent structures.[8] The fascial layer is anchored to the skin via suspensory ligaments, combined with subcutaneous fat and glandular tissue, ultimately responsible for the breast shape.

The breast receives blood from the internal mammary arteries, intercostal perforators, and axillary artery branches through perforating arteries. The deep venous system follows the arteries, and variable superficial venous drainage occurs. The lymphatic drainage is primarily directed towards the ipsilateral axilla and less towards the internal mammary or infraclavicular system.

The breast parenchyma comprises sac-like dilations known as ductules or acini lined by specialized cuboidal cells that produce milk in response to hormonal stimuli. A group of ductules is called a lobule, and they communicate through the intralobular terminal duct within a single lobule. The intralobular duct communicates with an extralobular duct known as the terminal ductal lobular unit. The terminal ductal lobular unit is the functional unit referred to in breast imaging and is the primary origin of breast cancer. Multiple terminal ductal lobular units form a breast lobe. A female breast has around 12 to 20 lobes identified by a single main draining duct that communicates with the nipple-areolar complex and stores milk within the lactiferous sinus.[9]

The axillary region is between the chest's lateral wall, the humerus's medial wall, and the scapula. The axillary nodes are organized by their positions relative to the pectoralis minor muscle. Level I nodes are found lateral to the lateral margin of the pectoralis minor, level II between the medial and lateral borders of the pectoralis minor, and level III nodes are found medial to the medial margin of the pectoralis minor.[10][11]

Indications

The Breast Imaging and Reporting System (BI-RADS), published by the American College of Radiology (ACR), provides a classification system for breast masses and recommendations for biopsy. The system for classifying cancer risk is based on imaging features and is assigned numerical values from 1 to 6. The higher the number, the more likely cancer is present. A breast biopsy is indicated in any patient with a complex cyst, solid mass, indeterminate or suspicious mass or microcalcifications, and architectural distortion.

A BI-RADS of 0 indicates that further evaluation is necessary, such as additional views or ultrasound; MRI is rarely needed for improved characterization.[12] BI-RADS 4A, 4B, and 4C, usually including masses and calcifications, suggest possible malignancy and warrant a biopsy and clip placement.

If the suspicious area is not visualized on breast ultrasound, a stereotactic mammographic breast biopsy and further radiologic evaluation of the specimen are warranted. Magnetic resonance-guided biopsy is recommended for lesions not well visualized on mammography. A breast radiologist compares the pathology with the imaging for concordance; if benign pathology is inconsistent with the imaging characteristics, further biopsy is recommended.[13]

Techniques continue to evolve. For example, radiomics is a quantitative analysis of the texture and shape of breast lesions within the grey values of images and provides a promising approach to predicting malignancy for BI-RADS 4 and 5 lesions. The radiomics score is combined with the BI-RADS category in a nomogram.[14]

Contraindications

A core biopsy is contraindicated for breast lesions measuring <5 mm in the longest dimension, as the procedure could remove the entire lesion.[15][16] Relative contraindications are overlying skin infections and a high risk of bleeding.

Contraindications for mammographic stereotactic guided biopsies include pregnancy, breast compression size, and barriers to proper positioning. Similar considerations apply to magnetic resonance-guided biopsy with the addition of implanted hardware.[17][18]

Equipment

The ACR and the United States government provide guidance and accreditation standards for breast imaging, including ultrasound, mammography, and magnetic resonance. Standards are regulated under an institution’s quality control program and are moderated by certified medical physicists or associates. 

Hand-held ultrasound machines in brightness mode produce images by intermittently transmitting ultrasonic waves through the probe and into a thin slice of tissue. The machine measures returning frequencies, amplitude, and time-to-return, and a series of mathematical calculations are performed and displayed as brightness levels on the monitor, usually in the form of an image.[19] Tissue composition, combined with the physical properties of the probe and technical factors, affects the image quality.

The mammographic-guided stereotactic biopsy machine is a specialized device that develops images using ionizing radiation. Some are designated for biopsies only, whereas others are components added to standard mammography machines. The biopsy examination apparatus, patient positioning, and software capabilities vary depending on the manufacturer.[20] Newer machines can perform tomosynthesis (3-D mammogram) guided biopsy.

MRI uses a combination of radiofrequencies and magnetic field strength to produce images; a supercooled electromagnet produces an adjustable magnetic field into which the patient is placed. The changes produced by coils and radiofrequency are measured and used to produce an image.[21] Specific MR biopsy protocols differ between institutions and specific scanners. While MR does not use ionizing radiation, a risk is associated with the magnetic field and its interactions with ferrous metal components such as implanted cardiac devices and neurostimulators. Image-guided biopsy techniques using nuclear medicine through gamma imaging and positron emission mammography are not commonly used.[22][23]

Personnel

The Mammography Quality Standards Act (MQSA), recently updated to include, among other things, notes on breast density,  publishes breast biopsy and accreditation requirements. A breast biopsy should be performed by a physician who understands the technology, the physics used to produce an image, the limitations of the technology, and common artifacts associated with breast imaging. Clinicians must demonstrate knowledge of breast anatomy and recognize physiologic breast changes and common breast pathologies.[24][25]

Preparation

Before biopsy, imaging is reviewed, and a strategy is created for patient positioning and approach to the lesion, including identifying structures such as blood vessels and breast implants. All protocols require a patient to remain still for at least 1 hour. Stereotactic positioning can be prone, upright, or lateral decubitus.[26] Most magnetic resonance-guided biopsies are performed with the patient in the prone position.[20] Ultrasound-guided breast biopsies are usually performed with the patient lying supine to slightly anterior oblique on an examination table. To reduce tissue shifting due to gravity, the side to be evaluated is elevated, and the ipsilateral arm is flexed over or under the head.[27] 

Technique or Treatment

Image-guided biopsies are obtained with ultrasound, mammography, or magnetic resonance. Biopsy specimens may be an aspirate or tissue. Fine-needle aspiration, which only yields cytology, is not reliable for the diagnosis of breast cancer but may be used on occasion to sample an atypical cyst or for lesions <0.5 cm in size.[28] This procedure introduces a 21- to 27-gauge beveled needle attached to a syringe into the target lesion in a to-and-fro motion using gentle negative pressure. The aspirate is placed on a slide and evaluated by a cytopathologist for sample adequacy. 

A vacuum-assisted core biopsy allows the biopsy mechanism to remain in place while obtaining several samples. During sampling, tissue is pulled into the aperture by vacuum pressure of 25 to 35 mm Hg and is then cut by the blade. The sample is aspirated into a collection reservoir, which is emptied periodically. The process is repeated until an adequate sample has been obtained.[29][30]

Spring-loaded core needle biopsy devices are simple to use and inexpensive. This method is useful for sampling separate lesions within the same breast quadrant, but some local trauma is associated with multiple needle sticks. The stylet in the biopsy device is propelled forward from the potential energy stored within the spring, called a throw. The throw can be adjusted from 0.5 to 2.5 cm. Like the vacuum device, a cutting cannula is deployed over the aperture, and a sample is taken. The device is removed, and tissue samples are collected by discharging the aperture and rolling the device onto a sterile gauze or into a tissue cup. This process can be repeated as needed.[31][32] 

Ultrasound-Guided Biopsy 

The advantages of ultrasound are faster procedural time and lack of both ionizing radiation and breast compression. Some lesions are not well visualized on ultrasound. The machine should be programmed for breast imaging.[33] Further technical discussion is beyond the scope of this paper. The overlying skin and deeper tissue are anesthetized.[34] While visualizing the target lesion, the needle is advanced into the breast, maintaining the needle trajectory parallel to the chest wall. After the biopsy aperture is visualized within the target lesion, the image is saved for post-biopsy review.

Generally, 4 to 10 samples are obtained. A marker is placed at the biopsy site, and manual pressure is applied to mitigate the formation of a hematoma. A post-biopsy mammogram is obtained and compared to pre-biopsy imaging to confirm the biopsy site and marker placement.[35][36] 

Mammography-Guided Biopsy

The advantage of mammographic-guided biopsy is the ability to target lesions poorly visualized on ultrasound, such as microcalcifications. The disadvantages include cost, procedure time, and exposure to ionizing radiation.

The breast is placed between a compression plate and an imaging receptor, and a scout image image is obtained at 0º. If the lesion is seen within this image, subsequent images are obtained at 15º and -15º relative to the scout.[20] The skin and underlying tissue is anesthetized. Some institutions repeat the scout images to ensure the lesion has not moved. After the lesion’s location is confirmed, a skin incision is made, and the biopsy needle is advanced to the desired depth via the coordinate system. A second set of images is obtained to confirm needle positioning. Tissue sampling is performed along multiple axes for 6 to 12 samples. Before removing the biopsy device, the tissue samples are evaluated under x-ray to ensure the target lesion was sampled. 

When adequate sampling has been confirmed, the biopsy device is removed, and a biopsy marker is placed. The patient is removed from the mammogram, and pressure is applied to the biopsy site. A post-biopsy mammogram is obtained to ensure accurate sampling and proper biopsy marker placement.[27][29] 

Magnetic Resonance-Guided Biopsy

Magnetic resonance (MR)-guided biopsy is reserved for lesions detected only by MR. This imaging modality lacks the ionizing radiation of mammography but is also the most costly and time-consuming. MR-guided biopsy is most accurate for ductal lesions. 

The patient is placed in the prone position. The breast is compressed and prepped similarly to a mammographic stereotactic biopsy. The biopsy is taken from the lateral to the medial aspect of the breast. Sagittal T1 fat saturation pre- and post-contrast sequences are obtained. The needle is advanced within the sagittal plane under intermittent image guidance. This process is repeated until positioning is confirmed. Then, as in mammographic stereotactic biopsies, a vacuum or spring-loaded device takes 6 to 12 samples. The needle is removed, a biopsy marker is placed, and compression is applied. A post-biopsy mammogram is performed to confirm biopsy marker placement.[37][38] 

Complications

The most common complications of stereotactic and needle breast biopsies are ecchymoses, hematoma, and biopsy marker migration. Hemothorax, pneumothorax, or hemopneumothorax can occur, but these can usually be avoided with good technique.[39] Implant ruptures occur on rare occasions.[29][30][37]

Clinical Significance

The ability to procure an accurate and detailed tissue diagnosis for breast cancer, including tumor size, tumor markers, invasiveness, nodal status, and presence of metastatic disease, is imperative to providing the most effective therapy. The ability to review imaging concurrently with the histopathology of a biopsy specimen allows for the application of precision treatment. While the tumor remains in situ, additional imaging and biopsies can be performed.

Enhancing Healthcare Team Outcomes

Breast cancer is the most common cancer affecting women worldwide, with increasing incidence in women younger than 50 years in industrialized nations and higher mortality in underdeveloped areas, often due to advanced stage at the time of diagnosis. Collecting greater detail regarding tumor biology and genetic markers has allowed for more precise, personalized therapy implementation.[40][41] The care of persons with breast cancer is complex and requires interprofessional collaboration, which has resulted in decreased mortality.[42] This collaborative approach involving physicians, advanced practitioners, nurses, pharmacists, and other health professionals is vital to ensure patient-centered care, optimal outcomes, patient safety, and team performance. Each healthcare team member brings unique skills and expertise to the table, contributing to a comprehensive and multidisciplinary approach.

Physicians play a pivotal role in overseeing the biopsy procedure, providing clinical expertise in diagnosing and managing breast conditions. Their skills involve accurately interpreting imaging studies, identifying suitable candidates for biopsy, and accurately performing procedures to obtain tissue samples. Advanced practitioners, such as nurse practitioners or physician assistants, complement this role by assisting in patient evaluation, counseling, and postprocedure care. Their involvement enhances accessibility to care and contributes to timely interventions.

Nurses are essential for patient advocacy, education, and procedural support throughout the biopsy process. Their skills in patient assessment, communication, and coordination help alleviate anxiety, ensure patient comfort, and monitor for any complications. Pharmacists contribute by reviewing medication histories and providing medication management post-biopsy to optimize recovery and pain management.

Each team member's responsibilities extend beyond their specific roles to encompass effective interprofessional communication and collaboration. Clear communication ensures that pertinent clinical information is shared, concerns are addressed promptly, and care transitions are seamless. By fostering a culture of mutual respect and collaboration, healthcare professionals can optimize patient outcomes and enhance team performance.

Care coordination is paramount in providing comprehensive care across the continuum, from pre-biopsy evaluation to postprocedure follow-up. Health professionals must coordinate appointments, tests, and consultations to ensure that patients receive timely and integrated care. By streamlining workflows and leveraging technology, care coordination minimizes delays, reduces errors, and improves overall efficiency.

Following successful breast cancer treatment, patients remain at an elevated risk for developing new breast cancer compared to the baseline population; surveillance remains essential in this population.[43] Primary care clinicians facilitate timely monitoring.[44] The interprofessional team helps decrease morbidity and mortality from breast cancer through access to care, planning, and communication.[45]