Aetna considers any of the following minimally invasive image-guided breast biopsy procedures medically necessary as alternatives to needle localization core surgical biopsy (NLBx) in members with abnormalities identified by mammography that are non-palpable or difficult to palpate (i.e., because they are deep, mobile, small (less than 2 cm), or are composed of clustered microcalcifications):

1. Advanced Breast Biopsy Instrument (ABBI); or
2. Stereotactically guided core-needle biopsy; or
3. Ultrasound-guided core-needle biopsy; or
4. MRI-guided core-needle biopsy; or
5. Vacuum assisted core-needle biopsy (Mammotome™ device).

Aetna considers other minimally invasive image-guided breast biopsy procedures (i.e., those not mentioned above) experimental and investigational (e.g., PET-guided breast biopsy (Naviscan)) because their effectiveness has not been established.

Aetna considers radioactive seed localization for breast lesion/cancer experimental and investigational because its effectiveness has not been established.

Aetna considers tomosynthesis-guided localization/biopsy experimental and investigational because its effectiveness has not been established.

See also CPB 0071 - Positron Emission Tomography (PET), CPB 0105 - Magnetic Resonance Imaging (MRI) of the Breast, and CPB 0517 - Breast Ductal Lavage and Fiberoptic Ductoscopy.

Recent comparative studies have demonstrated several advantages of minimally invasive breast biopsy procedures over needle localization core surgical biopsy (NLBx).  Minimally invasive breast biopsy procedures take less time to perform than NLBx, cause less patient discomfort and cosmetic deformity, result in less artifact on subsequent mammography, and are more cost effective.  If a benign lesion is found, the patient can be followed with clinical examinations and mammography and an open surgical procedure is avoided.

Biopsies can be obtained either with a fine-needle (20-gauge) or large bore (11- and 14-gauge) needle.  However, the large-core biopsy is favored over fine-needle biopsy for several reasons: (i) large core biopsy samples can be interpreted by pathologists who do not have special training in cytopathology; (ii) specimens obtained by large core biopsy are more likely to be sufficient than those obtained by fine-needle biopsy; (iii) large core biopsy samples allow the pathologist to differentiate in-situ from invasive carcinoma; and (iv) pathologists can characterize lesions more completely with large-core biopsy samples.

For larger, fixed, palpable lesions, image guidance is considered not medically necessary for performing an adequate biopsy.  In these cases, palpation-guided biopsy is sufficient for locating the lesion and obtaining an adequate tissue sample.  However, image-guidance has been shown to be useful for directing the biopsy of non-palpable or vaguely palpable lesions.  The Center for Medicare and Medicaid Services (CMS, 2002) concluded that imagine-guided biopsy may be indicated for lesions that are non-palpable or vaguely palpable, and that “clinical studies suggest that such lesions may include those that are vaguely palpable, mobile, deep, or small, particularly less than 2 cm.  Palpable lesions that demonstrate a small area of clustered microcalcifications on a mammogram may be difficult to biopsy using palpation alone and thus may warrant image-guided biopsy.  Lesions that are difficult to biopsy using palpation are generally those that border on being non-palpable; non-palpable lesions are not amenable to palpation-guided biopsy.”

Hanna et al (2005) stated that stereotactic breast biopsy techniques minimize the surgical trauma associated with conventional wire-guided open breast biopsy for non-palpable breast lesions (NPBLs).  Advanced breast biopsy instrumentation (ABBI) allows for a 2-cm core of breast tissue to be excised under stereotactic guidance in an outpatient setting.  These investigators reported their initial experience with ABBI.  Hospital charts from 89 ABBI procedures between October 1996 and July 2002 were retrospectively reviewed for patient characteristics, ABBI parameters, radiographic appearance, pathology, complications, and clinical follow-up.  Data were presented as percentage/median (range).  Median age was 59 years (range of 39 to 80 years), mammographic lesions were classified as calcifications 49 % (44/89), soft tissue 39 % (35/89), or mixed 11 % (10/89).  Median radiographic size was 7 mm (1 to 60 mm).  Final pathology revealed ductal carcinoma in situ (DCIS) in 7 % (6/89) and invasive cancer in 22 % (20/89).  Microscopically clear margins were obtained in 55 % (11/20) of patients with invasive cancer.  Of these, 82 % (9/11) chose not to undergo further local surgical therapy.  Eight patients remain disease free at 56 months (range of 41 to 95 months) follow-up.  The 9th patient was deceased at 6 months from an unrelated cause.  The overall complication rate was 3 % (3/89).  A definitive diagnosis was obtained in 100 % of malignant and 87 % of benign cases.  Median waiting time was 19 days (range of 0 to 90 days).  The authors' experience demonstrated that ABBI is an effective diagnostic tool for NPBLs.  It is associated with minimal complications, and provides negative margins in over 50 % of malignant cases.  In selected patients with invasive cancer and negative margins, ABBI may obviate the need for further local surgical treatment.  Furthermore, ABBI merits additional investigation as a therapeutic modality for early breast cancer.

Szynglarewicz et al (2011) compared the procedure duration time for different methods of minimally invasive image-guided vacuum-assisted breast biopsy (VABB).  A total of 691 women with non-palpable breast masses classified as BI-RADS IV or V were studied.  All of them underwent minimally invasive percutaneous VABB with an 11-gauge needle.  In 402 patients an ultrasound-guided procedure with a hand-held device was performed while in 289 women stereotactic biopsy was carried out using a dedicated prone table unit with digital imaging.  In each case the duration of biopsy was measured in terms of the total procedure time, room time and physician time.  There were no significant differences between the stereotactic and ultrasound-guided groups with regard to patient age, body mass index, menopausal status, history of parity, hormone replacement therapy, breast parenchymal pattern (according to Wolfe's classification), family history of breast cancer, mass size and number of samples.  Ultrasound-guided biopsy was found to take significantly less time than prone stereotactic biopsy in every aspect of procedure duration.  Mean total procedure time, room time, and physician time in minutes were 26.7 ± 8.2 versus 47.5 ± 9.4 (p < 0.01), 23.1 ± 8.5 versus 36.5 ± 9.2 (p < 0.05), and 12.3 ± 5.6 versus 18.6 ± 5.9 (p < 0.05), respectively.  The authors concluded that ultrasound-guided breast biopsy is less time-consuming than the stereotactic procedure for both the patient and the physician.  Because of the shorter procedure time (as well as other well-known advantages: real-time imaging, lower cost), ultrasound-guided biopsy should be considered the method of choice for sampling suspicious nonpalpable breast masses.

Radioactive seed localization (RSL) has also been advocated as a means to facilitate the operative excision of non-palpable breast lesions, and appears to be a new option for women undergoing lumpectomies.  With this procedure, a radiologist places a very low-energy radioactive seed into the abnormal tissue or tumor, guided by mammography.  During the surgery, the surgeon uses a hand-held Geiger counter to more precisely identify the location of the tumor.  The Geiger counter also allows the surgeon to obtain a three-dimensional (3-D) view of the tumor’s location.  On the day of the lumpectomy, the patient arrives about 2 hours before the surgery to receive light sedation and a local anesthetic to numb the surgical area.  After the surgeon removes the abnormal tissue or tumor along with the radioactive seed, the incision is closed and bandaged.  Once the seed is removed with the breast tissue, the radioactivity is gone.  The patient is able to leave the hospital later that same day. 

Rao et al (2010) stated that seed localization uses a radioactive source to identify non-palpable breast lesions for excision; it is an emerging alternative to wire-localized breast biopsy (WLBB).  Previous single health system studies reported decreased rates of re-excision and improved patient convenience with this technique.  This study was the first to implement this procedure in a public health care delivery system composed of a primarily minority and low-income population.  A multi-disciplinary team was formed to create a protocol for RSL and monitor the results.  After 50 RSL were successfully completed, a retrospective matched-pair analysis with patients who had undergone WLBB during the same period was performed.  Overall experience with the RSL protocol was reviewed, along with the occurrence of a seed loss.  Processes necessary to re-activate the RSL protocol and prevent future losses were delineated.  Radioactive seed localization is associated with decreased rates of re-excision and can be successfully implemented in a public health care system.  The authors concluded that RSL is an attractive alternative to WLBB in a high-volume, county-based population.  It allows increased efficiency in the operating room and has a low rate of complications.  Cautionary measures must be taken to ensure proper seed chain of custody to prevent seed loss.

Jakub et al (2010) noted that WLBB remains the standard method for the surgical excision of non-palpable breast lesions.  Because of many of its shortcomings, most important a high microscopic positive margin rate, alternative approaches have been described, including RSL.  These investigators highlighted the literature regarding RSL, including safety, the ease of the procedure, billing, and oncologic outcomes.  Medline and PubMed were searched using the terms "radioactive seed" and "breast".  All peer-reviewed studies were included in this review.  The authors concluded that RSL is a promising approach for the resection of non-palpable breast lesions.  It is a reliable and safe alternative to WLBB.  Radioactive seed localization is at least equivalent compared with WLBB in terms of the ease of the procedure, removing the target lesion, the volume of breast tissue excised, obtaining negative margins, avoiding a second operative intervention, and allowing for simultaneous axillary staging.

McGhan et al (2011) performed a retrospective review of all consecutive RSL procedures performed at a single institution from January 2003 through October 2010.  A total of 1,000 RSL breast procedures were performed in 978 patients.  Indications for RSL included invasive carcinoma (52 %), in-situ carcinoma (22 %), atypical hyperplasia (11 %), and suspicious percutaneous biopsy findings (15 %).  A total of 1,148 seeds were deployed using image guidance, with 76 % placed greater than or equal to 1 day before surgery.  Most procedures (86 %) utilized 1 seed.  A negative margin was achieved at the first operation in 97 % of patients with invasive carcinoma and 97 % of patients with ductal carcinoma in-situ (DCIS).  An additional 9 % of patients with invasive carcinoma and 19 % of patients with DCIS had close (less than or equal to 2 mm) margins, and underwent re-excision.  Sentinel lymph node biopsy was successfully performed in 99.8 % of cases.  Adverse events included 3 seeds (0.3 %) not deployed correctly on first attempt and 30 seeds (2.6 %) displaced from the breast specimen during excision of the targeted lesion.  All seeds were successfully retrieved, with no radiation safety concerns.  Local recurrence rates were 0.9 % for invasive breast cancer and 3 % for DCIS after mean follow-up of 33 months.  There was no evidence of a learning curve.  The authors concluded that RSL is a safe, effective procedure that is easy to learn, with a low incidence of positive/close margins.  They stated that RSL should be considered as the method of choice for localization of non-palpable breast lesions.  The main drawback of this study was its retrospective, non-randomized design.

Lovrics et al (2011) examined if radio-guided localization surgery (RGL) (radio-guided occult lesion localization [ROLL] and RSL) for non-palpable breast cancer lesions produces lower positive margin rates than standard WLBB surgery.  These researchers performed a comprehensive literature review to identify clinical studies using either ROLL or RSL; included studies examined invasive or in-situ breast cancer, and reported pathologically assessed margin status or specimen volume/weight.  Two reviewers independently assessed study eligibility and quality and abstracted relevant data on patient and surgical outcomes.  Quantitative data analyses were performed.  A total of 52 clinical studies on ROLL (n = 46) and RSL (n = 6) were identified; 27 met inclusion criteria: 12 studies compared RGL to WLBB and 15 studies were single cohorts using RGL.  A total of 10 studies were included in the quantitative analyses.  Data for margin status and re-operation rates from 4 randomized controlled trials (RCT; n = 238) and 6 cohort studies were combined giving a combined odds ratio (OR) of 0.367 and 95 % confidence interval (CI): 0.277 to 0.487 (p < 0.001) for margins status and OR 0.347, 95 % CI: 0.250 to 0.481 (p < 0.001) for re-operation rates.  The authors concluded that the findings of this systematic review of RGL versus WLBB demonstrated that RGL technique produces lower positive margins rates and fewer re-operations.  While this review was limited by the small size and quality of RCTs, the odds ratios suggested that RGL may be a superior technique to guide surgical resection of non-palpable breast cancers.  They stated that these results should be confirmed by larger, multi-centered RCTs.

Langhans et al (2012) stated that the Danish national mammography screening program leads to identification of an increased number of small non-palpable breast tumors, suitable for breast-conserving surgery.  Accurate lesion localization is therefore important.  The current standard is WLBB and although effective it involves a risk of high rates of positive margin and re-operations.  New methods are emerging and RSL seems promising with regards to re-operation rates and logistics.  In RSL, a small titanium seed containing radioactive iodine is used to mark the lesion.

The National Comprehensive Cancer Network (NCCN, 2012) clinical practice guideline on breast cancer does not mention the use of RSL.

Hahn and colleagues (2012) stated that the vacuum biopsy of the breast under sonographic guidance (VB) was introduced in Germany in the year 2000 and the first consensus recommendations were published by Krainick-Strobel et al in 2005.  Since then, many clinical studies on this technique have been published.  These investigators updated the consensus recommendations from 2005 regarding the latest literature.  The consensus statements were the result of 2 preliminary meetings after the review of the latest literature by members of the Minimally Invasive Breast Intervention Study Group from the German Society of Senology.  The final consensus text was review by all members of the work group.  The statements listed under results obtained complete acceptance (consensus 100 %).  The consensus recommendations described the indications, investigator qualifications, technical requirements, documentation, quality assurance and follow-up intervals regarding the latest literature.  The authors concluded that the VB is a safe method for extracting breast tissue for histological work-up.  The technique allows the resection of breast tissue up to 8 cm3.  Besides the diagnostic indications, the method qualifies for a therapeutic resection of symptomatic benign lesions (e.g., fibroadenomas).  The technique should be used in specialized breast centers working in a multi-disciplinary setup.

Kibil et al (2013) evaluated the value of the mammography-guided and ultrasound-guided vacuum-assisted core biopsy in the diagnosis and treatment of intra-ductal papillomas of breast and answered the question if Mammotome biopsy allows avoidance of surgery in these patients.  In the period 2000 to 2011, a total of 2,246 vacuum-assisted core biopsies were performed, of which 1,495 were ultrasound-guided and 751 were mammography-guided (stereotaxic).  In 76/2,246 patients (3.4 %), aged 19 to 88 years (mean age was 51.5) histopathological examination confirmed intra-ductal papilloma.  Atypical lesions were accompanying intra-ductal papilloma in 16/76 cases (21 %).  Open surgical biopsy performed in these group revealed invasive cancer in 3 women.  In all 60 cases (79 %) with benign papilloma in biopsy specimens, further clinical observation did not show recurrence or malignant transformation of lesions.  The authors concluded that vacuum-assisted core biopsy is a minimally invasive and efficient method used for diagnosing intra-ductal papilloma of the breast.  If histopathological examination confirms a benign character of the lesion, surgery may be avoided but regular follow-up is recommended.  However in all cases, histopathologic diagnosis of papilloma with atypical hyperplasia or a suspected malignant lesion in imaging examinations, despite negative biopsy results, should always be an indication for surgical excision.

The use of tomosythesis to guide breast procedures such as localization/biopsy is currently under investigation.  Breast tomosynthesis, also called 3-D breast imaging, is a mammography system where the x-ray tube moves in an arc over the breast during the exposure.  It creates a series of thin slices from which numerous projection images are obtained.  Data from these projection images are then manipulated using reconstruction algorithms similar to computed tomography (CT) scans to produce thin-slice cross-sectional images through the breast.  The manufacturer of the Affirm Breast Biopsy Guidance System (Hologic, Inc., Danbury, CT) states that “the biopsy option allows radiologists to locate and accurately target regions of interest for biopsy using tomosynthesis” (Hologic, 2012).  However, the published peer-reviewed scientific literature has not demonstrated the accuracy and clinical utility of 3-D digital tomosynthesis.  However, there is insufficient evidence to support the effectiveness and clinical utility of this approach.

Viala et al (2013) described their operating process and reported results of 118 stereotactic vacuum-assisted biopsies performed on a digital breast 3D-tomosynthesis system.  Informed consent was obtained for all patients.  A total of 106 patients had a lesion, 6 had 2 lesions.  Sixty-one lesions were clusters of micro-calcifications, 54 were masses and 3 were architectural distortions.  Patients were in lateral decubitus position to allow shortest skin-target approach (or sitting).  Specific compression paddle, adapted on the system, performed, and graduated, allowing localization in X-Y.  Tomosynthesis views defined the depth of lesion.  Graduated Coaxial localization kit determined the beginning of the biopsy window.  Biopsies were performed with an ATEC-Suros, 9-G hand-piece.  All biopsies, except 1, had reached the lesions.  Five hemorrhages were incurred in the process, but no interruption was needed; 8 breast hematomas all resolved spontaneously; 1 was an infection.  About 40 % of patients had a skin ecchymosis.  Processing was fast, easy, and required lower irradiation dose than with classical stereotactic biopsies.  Histology analysis reported 45 benign clusters of micro-calcifications, 16 malignant clusters of micro-calcifications, 24 benign masses, and 33 malignant masses.  Of 13 malignant lesions, digital 2-D mammography failed to detect 8 lesions and under-estimated the classification of 5 lesions.  Digital breast 3-D tomosynthesis depicted malignant lesions not visualized on digital 2-D mammography.  The authors concluded that development of tomosynthesis biopsy unit integrated to stereotactic system will permit histology analysis for suspicious lesions.

An UpToDate review on “Breast imaging: Mammography and ultrasonography” (Venkataraman and Slanetz, 2014) states that “Breast tomosynthesis (also known as “3-D mammography”) has been approved by the US Food and Drug Administration for routine clinical use as an adjunct to standard mammography.  Tomosynthesis is a modification of digital mammography and uses a moving x-ray source and digital detector.  A three dimensional volume of data is acquired and reconstructed using computer algorithms to generate thin sections of images …. The examination has a slightly longer exposure time of 10 seconds per acquisition compared to standard digital mammography, which could increase the radiation dose per acquisition and increase the risk of motion artifacts.  At present, tomosynthesis is approved only to be performed in conjunction with a conventional mammogram.  Hence, when performed in the screening setting, the patient is exposed to approximately twice the usual radiation dose, which sometimes is greater if the patient had dense or thick breasts.  This technique shows promise in screening women with dense breast tissue and with high risk for breast cancer, although there are no prospective large studies to justify its routine use at the present time”.   Furthermore, an, UpToDate review on “Breast biopsy” (Esserman and Joe, 2014) does not mention the use of tomosynthesis-guided biopsy.