Pending Policies - Surgery


Breast Ductal Lavage or Ductoscopy

Number:SUR716.019

Effective Date:05-15-2018

Coverage:

This medical policy has become inactive as of the end date above.  There is no current active version and is not to be used for current claims adjudication or business purposes.

*CAREFULLY CHECK STATE REGULATIONS AND/OR THE MEMBER CONTRACT*

Breast Ductal Lavage or Suction Collection

Breast ductal lavage of the mammary ducts, including suction collection, to perform epithelial cell cytology on nipple aspirate fluid (NAF) is considered experimental, investigational and/or unproven for any indication, including breast cancer screening, assessment of breast cancer risk and managing patients at high-risk of breast cancer.

Breast Ductoscopy

Breast ductoscopy or “fiberoptic” ductoscopy is considered experimental, investigational and/or unproven for any indication, such as:

A combination with cytology evaluation for patients who have nipple discharge without a palpable mass; or

An evaluation of the mammary ducts for breast cancer screening or breast cancer risk assessment.

Virtual Ductoscopy

Breast ductoscopy, using computed tomography (CT) as “virtual ductoscopy” imaging, with collection of NAF by an additional modality or without NAF as a scan, for diagnostic measure, is considered experimental, investigational and/or unproven.

Description:

Cytologic analysis of epithelial cells from individual mammary ducts is a technique that has been investigated as a diagnostic and risk assessment tool in patients at higher than normal risk of breast cancer but without mammographic abnormalities. For example, the finding of atypical hyperplasia may be associated with an increased risk of breast cancer. Malignant cells may also be identified in rare cases.

Breast Ductal Lavage or Suction Collection

Physicians and patients use the results from ductal lavage to weigh the risks and benefits of a variety of management options. These options include closer surveillance, chemoprevention therapy (i.e., Tamoxifen) and in very high-risk women, even consideration of prophylactic mastectomy. Techniques to obtain the epithelial cells from nipple fluid aspirations include ductal lavage or suction collection. These techniques are commonly known as the “breast pap smear”.

Breast ductal lavage of the mammary ducts involves the following steps:

1. Fluid-yielding mammary ducts are identified using nipple aspiration;

2. A micro-catheter is inserted into the natural nipple opening of the identified individual mammary duct;

3. Saline is infused and ductal fluid withdrawn; and

4. The fluid is analyzed microscopically for cytologic abnormalities.

Breast suction collection of the mammary ducts involves the following steps:

1. Small breast cups are placed on the breasts and adjusted to fit;

2. The system engages and automatically warms the breasts;

3. The system applies light suction followed by compression to bring nipple aspirate fluid (NAF) to the surface (similar to that of a breast pump used for lactating breasts); and

4. The fluid is analyzed microscopically for cytologic abnormalities.

Regulatory Status

The following table is a summary of the approved U.S. Food and Drug Administration (FDA) ductal lavage or suction devices.

Device

FDA Approved

Known Additional Names

Pro Duct Health Micro Stylet®

May 2000 for Marketing Device

InDuct™ Breast MicroAspirator, Pro Duct or InDuct MicroCatheter, Breast Duct Stylet or InDuct MicroDialator

HALO™ NAF (Nipple Aspirate Fluid) Collection System

November 2005 for Marketing Device

HALO Breast Pap Test, HALO Breast Cancer Test

FirstCyte® Breast Test

December 2006 for Marketing Device

FirstCyte Aspirator, Microcatheter, Cytyc, and Dilator

NOTE 1: Several of the devices listed above may be in used in any ongoing clinical trial.

NOTE 2: In February 2013, the FDA issued a warning letter to Atossa Genetics, Inc. (Seattle, WA, USA) for marketing its nipple aspirate test for uses not approved by the FDA. In October 2013, Atossa Genetics issued a voluntary recall of its ForeCYTE Breast Health Test and Mammary Aspiration Specimen Cytology Test (MASCT). The MASCT has been known as the “Breast Aspirator”. The FDA classified these tests as a Class I recall, reserved for dangerous or defective products and have a reasonable chance of causing serious health problems or death. The MASCT was originally FDA approved for Marketing in December 2001.

The FDA will continue to monitor the promotional activity of nipple aspirate test manufacturers having NAF test kits still available for marketing.

Breast Ductoscopy

Breast ductoscopy is also known as mammary/breast duct endoscopy, fiberoptic ductoscopy/mammoscopy, or intraductal approach. Breast ductoscopy describes an emerging technique that allows direct visual access of the ductal system of the breast through nipple orifice cannulation and exploration. Saline can also be injected and extracted for examination by cytology.

The technique has been investigated in the following clinical conditions:

Diagnostic technique in patients with spontaneous nipple discharge, where endoscopy might function as an alternative to surgical incision (such as intraductal breast biopsy) or as a modality to perform breast ductal lavage;

Diagnostic technique to obtain cellular material to stratify women for risk of breast cancer;

Follow-up test for patients with atypical cytology as detected by breast ductal lavage;

Delineation of intraductal disease to define margins of surgical resection; and/or

The direct delivery of therapeutic agents, including photodynamic therapy, laser ablation, topical biologic agents, etc.

Regulatory Status

The following table is a summary of the approved FDA devices and those in any clinical trials which are currently being used.

Device

FDA Approved

Known Additional Names

ViaDuct™ MicroEndoscope®

July 2001 and May 2004 for Marketing Device

Miniaturized Biopsy Scope, ViaDuct™ Miniscope, Acueity System

Virtual Ductoscopy

“Virtual ductoscopy” imaging, which is a three-dimensional (3-D) reconstruction technique using computed tomography (CT) scans of the breast, is being investigated in clinical studies as another approach.

NOTE 3: Ductoscopy is not the same as ductogram or ductography (also known as galactogram or galactography), which is a radiograph or imaging technique of the mammary ducts after injection of a radiopaque substance directly into the duct system. Ductogram is used for investigating the pathology of nipple discharge.

Rationale:

This policy was created in 2002, based on clinical trial outcomes in addition to a 2002 Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessment. The policy updates were completed using searches of the MedLine database through February 2017. The following is a summary of the key literature to date.

Breast Ductal Lavage or Suction Collection

Validation of a diagnostic technology requires data regarding technical performance, diagnostic performance (i.e., sensitivity, specificity, and positive and negative predictive value) compared to a gold standard, and how the diagnostic information will be used in the management of the patient and whether beneficial health outcomes result.

Technical Performance - Nipple aspiration alone can be used to collect epithelial cells for cytologic analysis. Ductal lavage is designed to harvest an increased number of cells for analysis. In a multicenter clinical trial of 507 women who underwent nipple aspiration followed by ductal lavage, nipple aspiration produced an adequate sample in 27% of women, while ductal lavage produced an adequate sample in 78% of women. (1) A median of 13,500 cells per duct was collected by ductal lavage compared to a median of 120 epithelial cells per breast collected by nipple aspiration.

Diagnostic Performance - Dooley et al. reported on a multicenter clinical trial of 507 women who underwent ductal lavage. (1) A total of 57% of women had a prior history of breast cancer, and 39% had a five-year Gail Risk Model for breast cancer of 1.7% or more. It should be noted the patient selection criteria for this study are similar to those used in the large randomized trial of tamoxifen as a breast cancer chemoprevention therapy. Using a Gail Risk Model of greater than or equal to 1.7 %, all women over the age of 60 years would be considered at high-risk. For ductal lavage, 24% of women had abnormal cells that were mildly (17%) or markedly atypical (6%) or malignant (<1%). Ductal lavage detected abnormal cells 3.2 times more often than nipple aspiration. However, whether or not this increased sensitivity is accompanied by decreased specificity and thus a decreased overall risk of cancer using ductal lavage is unknown. It is difficult to identify a gold standard test to validate the diagnostic performance of ductal lavage. For example, since ductal lavage is performed in patients without mammographic abnormalities, there is no obvious target for diagnostic confirmation with a tissue sample. In cases where cells suspicious for malignancy have been reported, some patients may have undergone either surgical resection of the involved duct or a broader surgical resection. However, there have been no studies published regarding the diagnostic performance in this setting. No studies have been reported on the results of ductal lavage in patients with mammographic abnormalities who are scheduled to undergo biopsy.

How Diagnostic Information will be Used to Benefit the Management of Patients - Results of ductal lavage cytology can be broadly subdivided into those with an insufficient sample, those with malignant cells; those with hyperplasia, including atypical hyperplasia; or those with benign cells. Currently, no published studies have specifically used the results of ductal lavage to direct patient management.

The following discussion suggests some potential ductal lavage applications:

Insufficient Sample - There would be presumably no impact on the management of the patient when an insufficient sample was produced. Based on the preliminary results published, this would occur in about 22% of the patients.

Hyperplasia without Atypia - Hyperplasia is relatively common among high-risk women (31%–42%) and, to a somewhat lesser extent, among various populations of women not specifically selected to be at high-risk (12%–37%). Although hyperplasia without atypia is associated with increased cancer risk in some studies, its relatively high prevalence in both high- and low-risk populations decreases its utility as a risk marker.

Hyperplasia with Atypia - The association between histologic atypical hyperplasia and an increased risk of breast cancer has been most frequently studied in the setting of patients with mammographical abnormalities. The natural history of atypical hyperplasia may be different in women without mammographical abnormalities, potentially representing a spontaneously resolving cytologic abnormality. Two studies offer related data. Wrensch et al. reported on a prospective study of 2,701 white women at average risk of breast cancer who underwent nipple aspiration and then were followed up for an average of 12 years. (2) The relative risk of cancer in women with cytologic atypia was 4.9 compared to non-yielders of nipple fluid or 2.8 compared to women with normal cytology. In women with cytologic atypia and a family history, the relative risk was 18.1 compared to non-yielders of fluid without family history. After 21 years of follow-up, the relative risks were lower, suggesting that risk decreased over time. (3)

Fabian et al. reported on a group of 480 women without mammographic abnormalities who were considered at high-risk of breast cancer and who underwent two random periareolar fine-needle aspirations (FNA) at six month intervals. (4) Risk factors included a family history of breast cancer, a prior history of a precancerous lesion, such as atypical hyperplasia or carcinoma in situ, or a prior history of breast cancer. In 21% of patients, results of the FNA revealed atypical hyperplasia. After follow-up of 45 months, the relative risk of cancer in women with cytologic atypia was 5.0 compared to women without atypical results. The two strongest predictors of cancer development were risk assessment based on the Gail Risk Model and the presence of atypical hyperplasia on FNA.

The relative risk results for nipple aspiration or fine needle aspiration cytology (FNAC) have been equated with a relative risk of 5.3 in women with histologic atypia compared to women without proliferative disease on biopsy of a lesion, reported in a retrospective study. (5) However, due to the different follow-up intervals, different baseline risk populations studied, and different referent populations, these results cannot be quantitatively compared. Thus, it is not known whether cancer risk associated with cytologic atypia is of the same magnitude as cancer risk associated with histologic atypia on biopsy of a lesion.

Cytologic hyperplasia with atypia alone in low- to moderate-risk populations had poor sensitivity (4.2%) and low positive predictive value (13.8%). (3) Thus, this procedure has poor utility for general population screening to identify those at increased risk.

Clinical studies have suggested that even in the absence of mammographic abnormalities, atypical hyperplasia may be associated with an increased risk of breast cancer, both in patients at average and high-risk. For women already at high-risk of breast cancer by Gail Risk Model analysis, the following treatment options are available: increased surveillance, such as an increased frequency of breast self-examination or clinical exam; or an increased frequency of mammography, a prophylactic mastectomy, or chemoprevention with tamoxifen. Increased surveillance is recommended for all, and prophylactic mastectomy is considered only by relatively few women who have other strong risk factors, confirmed by BRCA1 (Breast Cancer 1) or BRCA2 (Breast Cancer 2) mutation. The net benefits of tamoxifen, taking into account possible adverse events, are greatest for women of younger age with greater Gail Risk Model, yet patients are reluctant to select chemoprevention. (6) For high-risk women with no history of histologic atypical hyperplasia of a biopsied lesion, it has been proposed that findings of cytologic atypia on ductal lavage may revise the risk estimate upward, increase the likelihood of choosing chemoprevention, and decrease cancer incidence. However, no studies have specifically explored decision making or outcomes regarding these treatment alternatives in mammographically normal women with atypical hyperplasia by cytologic analysis.

Chemoprevention with tamoxifen is suggested as a promising management strategy for atypical hyperplasia based on ductal lavage. Indirect evidence exists in the form of the National Surgical Adjuvant Breast and Bowel Project (NSABBP) P-1 trial, which randomized 13,388 high-risk patients, by using the Gail Risk Model greater than 1.7%, to receive either chemoprevention with tamoxifen or placebo. (7) The principal outcomes were the subsequent incidence of in situ or invasive cancer over the next five years. This trial reported that, overall, tamoxifen was associated with a 49% reduction in incidence of invasive breast cancer. When a history of atypical hyperplasia was present, tamoxifen was associated with an 86% reduction in the incidence of subsequent breast cancer. However, in this trial, atypical hyperplasia was presumably diagnosed in patients with mammographic abnormalities. While the results of the P-1 trial are statistically significant, there is a need to further refine the patient selection criteria for tamoxifen; for example, overall only 4% of the placebo group compared to 2% of the tamoxifen group developed breast cancer in the five-year time interval of the trial. In fact, results of the periareolar FNAC (specifically atypical hyperplasia) have been proposed as a potential technique for identifying those candidates most likely to benefit from tamoxifen. However, this strategy of patient selection has not been formally investigated. Whether or not women with cytologic atypia by ductal lavage benefit to the same extent is unknown. It is possible that knowledge of added risk as a result of cytologic analysis may influence those at greatest risk to choose tamoxifen therapy. It is also possible that knowledge of a negative cytologic analysis result would influence patients to avoid tamoxifen when they might otherwise benefit. No evidence exists to evaluate potential net benefit or harm in decision making or, ultimately, in patient outcomes.

The role of atypical hyperplasia as part of the decision making for prophylactic mastectomy is based on the hypothesis that atypia precedes the development of cancer. However, any patient with a confirmed BRCA1 or BRCA2 mutation may be considered a candidate for prophylactic mastectomy. The emergence of atypia may suggest a more immediate need for prophylactic mastectomy, and thus may affect the timing of the surgery. However, this strategy has not been formally tested.

Malignant cells - The results of the multi-institutional trial, currently summarized on the manufacturer's Web site (8), but not published in the peer-reviewed literature, report that malignant cells were identified in only two of 383 (0.5%) patients. Therefore, it is unlikely that ductal lavage will be routinely used to diagnose malignancy. In the rare event of malignant cells, imaging, ductogram, or ductoscopy are possible follow-up procedures, but a negative imaging result or ductogram does not exclude significant pathology and the overall sensitivity of ductography is unknown. The value of terminal duct excision is also unknown. Prophylactic mastectomy on the basis of a malignant lavage is not encouraged. (9)

Benign cells - Without an understanding of the sensitivity of ductal lavage, it is not possible to interpret a finding of benign cells, as this could represent a false-negative result.

The above conclusions were supported by the 2002 BCBSA TEC Assessment (10) that offered the following observations and conclusions:

No studies directly compare routine surveillance versus routine surveillance plus epithelial cell cytology analysis in the follow-up of high-risk women for the detection of long-term outcomes.

No studies compared the outcomes of patients whose management was determined by the results of routine surveillance vs. routine surveillance plus epithelial cell cytology analysis.

No studies have used ductal lavage, nipple aspiration, or random periareolar FNA to influence patient management in the population of interest.

There is some indirect evidence from the Breast Cancer Prevention Trial (P-1), which enrolled women at high-risk and randomly assigned them to placebo or tamoxifen for five-years. Women with a history of atypical hyperplasia who received tamoxifen had a risk ratio for subsequent breast cancer of 0.14, compared to those who received placebo over a median follow-up time of 54.6 months. Thus, high-risk women with a history of atypical hyperplasia benefited to a greater degree than the study population as a whole. It was noted, however, that the number of women in this subgroup was small, and that this was only one of five subgroups examined. Women without a history of atypical hyperplasia who received tamoxifen also benefited with a risk ratio of 0.56. Thus, the lack of a history of atypical hyperplasia does not preclude improved outcomes with tamoxifen treatment.

The results of the P-1 trial cannot address whether or not participants, particularly those with a negative history, had cytologic evidence of hyperplasia or atypical hyperplasia at the time of enrollment. It is possible that some of the women who were negative for a history of atypical hyperplasia would have been positive at study entry by random cytology, and may have accounted for at least part of the benefit in this subgroup. Nevertheless, it cannot be ruled out that women with no detectable atypical hyperplasia may still benefit from tamoxifen treatment.

Considering the above, the 2002 BCBSA TEC Assessment concluded that the evidence was insufficient to support the use of cytologic hyperplasia with atypia as a clinically useful intermediate biomarker outside of clinical trials at this time. The existing evidence is of high clinical interest, but further follow-up studies of risk and trials of intervention in women with this marker are needed.

Khan et al. published a study of 32 women who underwent ductal lavage in 44 breasts with known cancer prior to mastectomy. (11) In addition, ductal lavage was performed on eight breasts in seven women prior to prophylactic mastectomy, two of which were found to harbor occult cancer. The results of ductal lavage were compared with histologic specimens from the same lavaged ducts. The sensitivity of ductal lavage was 43% and the specificity was 96%. The authors hypothesize the low sensitivity of the test may be related to the fact that cancer contained in ducts fails to yield fluid or has benign or mildly atypical cytology. In a subsequent study focusing on women with microcalcifications, Khan reported that similar to patients with larger invasive cancers, smaller cancer, such as ductal carcinoma in situ (DCIS), often do not yield nipple fluid, leading to low sensitivity. (12) Brogi et al. reported the results of a similarly designed study of ductal lavage in 26 women scheduled to undergo mastectomy for breast cancer. Only 48% of the lavaged specimens revealed any evidence of atypia. (13) Johnson-Maddux et al. studied the reproducibility of cytologic atypia in repeat nipple duct lavage in 108 patients unselected for breast cancer risk. (14) Repeat lavage was performed in those with atypia found in the first lavage sample. Atypia was found in the second lavage sample in only 48% of cases. The authors concluded that the reproducibility of repeat lavage is low and that atypia may be either physiologic or artifactual.

A variety of review articles and commentaries have also been published that discuss potential applications of ductal lavage. (15, 16) Both of the Khan and Brogi articles (11, 12) cite the same studies as discussed in the 2002 BCBSA TEC Assessment. (10)

A number of publications were identified that questioned the technical and diagnostic performance of ductal lavage. One study assessed the reproducibility of repeated ductal lavage in 65 high-risk women. (15) Lavage was conducted in 162 (87%) matched ducts from 63 (97%) women at baseline and six-months. Over half of the matched ducts (51%) from 17 (27%) women were categorized as having an inadequate number of cells (<100) for morphologic diagnosis. When analyzed either per woman or per duct, there was poor agreement (kappa index from 0.14 to 0.130) between baseline and six-month follow-up for cell yield and cytologic diagnosis. The authors concluded that ductal lavage has limited utility for the serial monitoring of breast epithelium. Another study compares breast tissue acquisition by ductal lavage with random periareolar FNA (immediately following aspiration) in 86 women at high-risk for breast cancer. (16) Sample retrieval was successful in 100% of the women by needle aspiration, and 97% had adequate samples (ten or more epithelial cells). In contrast, samples were retrieved in only 51% of subjects using ductal lavage; the sample was considered adequate in 71% of these, resulting in a total yield of 31%. The authors concluded that FNA is a more practical option for clinical trials. A third study performed ductal lavage on 150 women (irrespective of the calculated risk level); 67 were patients with breast cancer. (17) Adequate samples (ten or more cells) for diagnosis were obtained from 90% of women but only 67% of ducts. Of 83 women without breast cancer, atypia was diagnosed in 34% of 44 women with a five year Gail Risk Model of <1.7% and 28% of women who had a five year Gail Risk Model of 1.7% or greater.

Visvanathan et al. (18) evaluated the reliability of nipple aspirate fluid (NAF) and ductal lavage at two time points six months apart in women (n=69) at increased risk for breast cancer. Eligible women had a five year Gail Risk of 1.66% or higher or lifetime risk of >20%, and/or a family history or personal history of breast cancer. All ducts that produced NAF were cannulated. Participants (mean age, 47 years) were enrolled over 35 months. Forty-seven returned for a second visit. Of the women who returned for a second visit, 18 of 24 who produced NAF had at least one duct successfully cannulated. Twenty-four ducts in 14 women were lavaged twice. Among these ducts, cellular yield for the two time points was inconsistent and only fair cytologic agreement was observed. The authors concluded that the use of ductal lavage is limited by technical challenges in duct cannulation, inconsistent NAF production, a high rate of inadequate cellular material for diagnosis, fair cytologic reproducibility, and low participant return rates.

Khan et al. (19) reported on a proof-of-principle phase II study to assess the utility of ductal lavage to measure biomarkers of tamoxifen action. The authors’ conclusions are as follows: “…we observed the expected changes in tamoxifen-related biomarkers; however, poor reproducibility of biomarkers in the observation group, the 53% attrition rate of subjects from recruitment to biomarker analyses, and the expense of ductal lavage are significant barriers to the use of this procedure for biomarker assessment over time.”

The ECRI Institute performed a report on ductal lavage and nipple aspiration, which is done to identify women at high risk for developing breast cancer. (20) Included in their review was the FDA warning described above. The overview of clinical literature from January 2009 through February 11, 2014 identified no systematic reviews/technology assessments, cost-effective analyses, or randomized clinical trials. Their review of 32 abstracts reported technical and scientific studies of nipple aspiration and ductal lavage. The abstracts did not report patient-oriented outcomes (e.g., breast cancer risk, pain). These studies were nonrandomized controlled/comparison studies, case series, and narrative reviews. There have no recent reviews by ECRI since the 2014 publication.

Ongoing and Unpublished Clinical Trials

A currently ongoing trial that might influence this policy is listed in Table 4.

Table 4. Summary of Key Trial

NCT Number

Trial Name

Planned Enrollment

Completion Date

Ongoing

NCT00028340

High-Risk Breast Duct Epithelium

184

Undetermined (recruiting)

Table Key:

NCT: National Clinical Trial.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN) Guidelines

The 2017 release of the NCCN guidelines on breast cancer risk reduction state (21), “The clinical utility and role of . . .nipple aspiration, or ductal lavage are still being evaluated and should only be used in the context of a clinical trial.”

American Society of Breast Surgeons (ASBS)

The ASBS no longer has an “official statement” regarding ductal lavage.

U.S. Preventive Services Task Force (USPSTF)

The USPSTF does not list breast ductal lavage, nipple aspiration, or suction collection as methods for breast cancer screening or risk assessment.

U.S. Food and Drug Administration (FDA)

In 2013, nipple aspirate tests have been voluntarily recalled by the manufacturer. This is the FDA safety communication statement (22), “The FDA is alerting the public, including women and health care providers, that a nipple aspirate test is not a replacement for mammography, other breast imaging tests, or breast biopsy, and should not be used by itself to screen for or diagnose breast cancer.”

According to the FDA, possible health consequences of stand-alone nipple aspirate testing for breast cancer include false negatives, causing providers to delay diagnosis and/or treatment for patients with breast cancer, and false positives, whereby patients face unnecessary anxiety and additional testing. The FDA is not aware of any scientific data that show nipple aspirate tests are effective screening tools for any medical condition, including the early detection of breast cancer or other breast disease. Note that the FDA regulates the marketing of kits for performing specific tests. Additional information can be found in the FDA website.

Section Summary: Breast Ductal Lavage or Suction Collection

In summary, the available literature regarding ductal lavage and suction collection systems for breast cancer risk assessment are inadequate to draw clinical conclusions. There are no new clinical trial outcomes or publications nor practice guidelines available that would permit a conclusion this method of breast cancer risk assessment be utilized outside of the clinical setting or as a substitute for mammography or other breast cancer screening modalities. These procedures are experimental, investigational and/or unproven for the assessment of breast cancer risk given the insufficient evidence to evaluate the impact on net health outcome.

Breast Ductoscopy

To date, ductal endoscopy had been used in pilot studies of women with spontaneous nipple discharge. There are no studies of breast duct endoscopy (ductoscopy) where focus has been on random examinations of high-risk women or that have compared ductoscopy with other breast cancer detection techniques. Reviews of the literature revealed published data suggest that breast duct endoscopy is feasible; however, there is minimal published information about how this procedure would be used in the management of the patient, such as determining the:

Need for other diagnostic testing (mammography or ductography), or

Need for biopsy or excision, or

Extent of the surgical excision.

Love and Barsky published a feasibility study in 1996, in which nine patients scheduled to undergo mastectomy first underwent ductoscopy. (24) The authors concluded the intraductal approach is feasible for the study of the early changes of breast cancer. Shen et al. studied the role of ductoscopy in 259 women with nipple discharge. (25) In 36% of patients, ductoscopy successfully identified an intraductal papillary lesion. Although the authors conclude that ductoscopy is a safe alternative to ductography in guiding subsequent breast surgery, there was no direct comparison between the two techniques. The same group of authors subsequently published a larger case series of 415 women with nipple discharge. Presumably, this study overlaps with the previous study. (26) An intraductal lesion was detected in 40% of the 166 patients; eleven were shown to have ductal carcinoma in situ (DCIS). While the authors concluded that ductoscopy may be a useful technique for diagnosis of DCIS prior to surgery, there are no data reporting on how the results of ductoscopy influence either the decision to undergo biopsy or excision, or influenced the extent of the excision. Dooley reported on a case series of 201 patients who underwent ductoscopy during a lumpectomy procedure. (27) The author concluded that ductoscopy could locate additional intraductal lesions outside the lumpectomy site, thus decreasing the incidence of a positive margin of resection. In a subsequent study, Dooley reported on a case series of 88 patients who underwent ductoscopy for nipple discharge or as a follow-up to a ductal lavage. (28) Many of these patients also had mammographic abnormalities. The authors concluded that medical office ductoscopy with biopsy is both feasible and does identify suspicious or malignant atypia in patients with expressed or spontaneous nipple fluid discharge. Sauter et al. and Matsunaga et al. has also documented the technical feasibility of ductoscopy in large a case series of patients with nipple discharge. (29, 30)

Improvements in the size of the endoscope, image quality, and method of sample collection for cytology are being reported. Given the rapid technological advances, most clinical studies are outdated by the time of publication. With this caveat in mind, two small prospective case series from Europe indicate that, in patients with nipple discharge, ductoscopy can effectively identify the location of a lesion but is not sufficiently sensitive for the diagnosis of malignancy. (31, 32) A retrospective review suggests that compared with major duct excision (140 patients) microductectomy (95 patients) detects a lower percentage of occult carcinoma; this may be related to the larger sample size of the resection specimen. (33) Newer methods may more effectively distinguish between benign and malignant lesions, potentially eliminating the need for unnecessary duct excision. This and other indications for breast duct endoscopy will need to be evaluated in larger trials.

Louie conducted a retrospective study of patients with nipple discharge who underwent ductoscopy and had a diagnosis of cancer. (34) In this small series of breast cancer patients, duct wall irregularities or intraluminal growths were noted during ductoscopy in 57% (8 of 14). The authors concluded that no clear morphologic changes noted during ductoscopy definitively indicated malignancy.

In a study from Europe, Hunerbein reported results using a new, rigid ductoscope during the evaluation of 66 patients with breast cancer and 45 patients with nipple discharge. (35) This new instrument is said to have improved optics as well as an approach for vacuum-assisted biopsy. In this case series, intraductal lesions were noted in 41% of patients with breast cancer. In addition, 16% of “normal” ducts had extensive intraductal lesions.

Grunwald et al. compared various diagnostic tests in patients with breast disease. (36) In this study, ductoscopy was compared to mammography, galactography, sonography, magnetic resonance imaging (MRI), nipple smear, FNAC, and high-speed core biopsy. However, not all patients received all evaluations; for example, only 19 patients had galactography. There were 71 ductoscopies that were followed up by open biopsies. Here, three invasive cancers and eight DCIS were found, as well as three atypical ductal hyperplasias, 44 papillomas or papillomatoses (all considered to be disease); and 13 benign findings. Feasibility of ductoscopy was 100% in this series. Duct sonography showed the highest sensitivity (67.3%), followed by MRI (65.2%), galactography (56.3%), ductoscopy (55.2%), and FNAC (67.3%). These highest specificity was shown by FNAC, core biopsy, and galactography (each 100%), followed by mammography (92.3%), nipple smear (77.8%), ductoscopy, and duct sonography (each 61.5%); the lowest specificity was displayed by MRI (25.0%). The authors believe that these results are promising and indicate that a multicenter European study is underway to further evaluate ductoscopy. Results were expected near the end of 2008.

In contrast to those results, in a study in China involving 1,048 women evaluated between 1997 and 2005, Liu identified 49 of 52 (94%) cancers among women presenting with spontaneous nipple discharge. (37) However, evaluation and follow-up was limited among the 489 cases that had normal ductoscopy and cytology. The authors note that 77 of these cases underwent tissue diagnosis within a median follow-up time of 19 months during which one malignancy (DCIS) was diagnosed.

In another paper from a European center, Jacobs et al. describes ongoing research and development in an attempt to have breast endoscopy become a potential therapeutic as well as a diagnostic approach. (38) The authors’ comment that these instruments, which require an additional working channel (for biopsies or brushings), are not presently available in the United States. Results for use of this technology are viewed as preliminary. Further studies are needed to better define both the clinical validity and clinical utility of this technique in appropriate populations.

Ongoing and Unpublished Clinical Trials

A currently ongoing trial that might influence this policy is listed in Table 5.

Table 5. Summary of Key Trial

NCT Number

Trial Name

Planned Enrollment

Completion Date

Ongoing

NCT01901562

Feasibility and Therapeutic Efficacy of Ductoscopic Papilloma Extraction in Patients with Pathologic Nipple Discharge

30

Jul 2017 (recruiting)

Table Key:

NCT: National Clinical Trial.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN) Guidelines

The 2016 release of the NCCN guidelines on breast cancer screening states, “Mammary ductoscopy is useful in evaluating patients who have nipple discharge, for accurate visualization, analysis, and excision of intraductal abnormalities.” (39) The NCCN guideline has not provided a recommendation or strength of evidence rating for this procedure.

American Society of Breast Surgeons (ASBS)

The ASBS does not have an “official statement” regarding ductoscopy.

U.S. Preventive Services Task Force (USPSTF)

The USPSTF does not list breast ductoscopy, fiberoptic ductoscopy, or virtual ductoscopy as methods for breast cancer screening or risk assessment.

Section Summary: Breast Ductoscopy

In summary, the available literature regarding breast ductoscopy for breast cancer screening and diagnosis are inadequate to draw clinical conclusions. The available published data consist of uncontrolled case series. (40, 41) There are no new clinical trial outcomes or publications nor practice guidelines available that would permit a conclusion this method of breast cancer screening or diagnosis be utilized outside of the clinical setting or as a substitute for mammography or other breast cancer screening modalities. These procedures are experimental, investigational and/or unproven in the evaluation and management of patients with suspected or known breast cancer given the insufficient evidence to evaluate the impact on net health outcome when compared to other available modalities.

Virtual Ductoscopy

One article in 2008 from Ichihara et al. discussed a new algorithm for 3D for refraction-based X-ray computed tomography (CT) for location and evaluation of DCIS. (44) Since then, there have not been any published studies to permit scientific conclusion regarding the role of virtual ductoscopy in the evaluation and management of patients with known or suspected breast cancer. This procedure is considered experimental, investigational and/or unproven because its impact on health outcomes is uncertain without prospective, randomized clinical trials.

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

19499

HCPCS Codes

None

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.

A national coverage position for Medicare may have been developed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

1. Dooley WC, Ljung BM, Veronesi U, et al. Ductal lavage for detection of cellular atypia in women at high-risk for breast cancer. J Nat Can Institute. Nov 7 2001; 93(21):1624-32. PMID 11698566

2. Wrensch MR, Petrakis NL, King EB, et al. Breast cancer incidence in women with abnormal cytology in nipple aspirates of breast fluid. Am J Epidemiol. Jan 15 1992; 135(2):130-41. PMID 1536131

3. Wrensch MR, Petrakis NL, Miike R, et al. Breast cancer risk in women with abnormal cytology in nipple aspirates of breast fluid. J Nat Can Institute. Dec 5 2001; 93(23):1791-8. PMID 11734595

4. Fabian CJ, Kimler BF, Zalles CM, et al. Short-term breast cancer prediction by random periareolar fine-needle aspiration cytology and the Gail risk model. J Nat Can Institute. Aug 2 2000; 92(15):1217-27. PMID 10922407

5. Dupon WD, Page DL. Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med. Jan 17 1985; 312(3):146-51. PMID 3965932

6. Port ER, Montgomery LL, Heerdt AS, et al. Patient reluctance toward tamoxifen use for breast cancer primary prevention. Ann Surg Oncol. Aug 2001; 8(7):580-5. PMID 11508619

7. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Nat Can Institute. Sep 16 1998; 90(18):1371-88. PMID 9747868

8. FirstCyte Breast Test – Product information. Marlborough, Maryland: Hologic Corporation (2007). Available at <http://www.hologic.com> (accessed on September 20, 2005).

9. Morrow M, Vogel V, Liung BM, et al. Evaluation and management of the woman with an abnormal ductal lavage. J Am Coll Surg. 2002; 194(5):648-56. PMID 12022606

10. Use of Epithelial Cell Cytology in Breast Cancer Risk Assessment and High-Risk Patient Management. Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center Assessment Program (2002 June) 17(1):1-33.

11. Khan SA, Wiley EL, Rodriquez N, et al. Ductal lavage findings in women with known breast cancer undergoing mastectomy. J Nat Can Institute. Oct 20 2004; 96(20):1510-7. PMID 15494601

12. Khan SA, Wolfman JA, Segal L, et al. Ductal lavage findings in women with mammographic microcalcifications undergoing biopsy. Ann Surg Oncol. Sep 2005; 12(9):689-96. PMID 16052275

13. Brogi E, Robson M, Panageas KS, et al. Ductal lavage in patients undergoing mastectomy for mammary carcinoma: A correlative study. Cancer. Nov 15 2003; 98(10):2170-6. PMID 14601086

14. Johnson-Maddux A, Ashfaq R, Cler L, et al. Reproducibility of cytologic atypia in repeat nipple duct lavage. Cancer. Mar 15 2005:1129-36. PMID 15685620

15. Patil DB, Lankes HA, Nayer R, et al. Reproducibility of ductal lavage cytology and cellularity over a six-month interval in high risk women. Breast Can Res Treat. Nov 2008; 112(2):327-33. PMID 18097749

16. Arun B, Valero V, Logan C, et al. Comparison of ductal lavage and random periareolar fine needle aspiration as tissue acquisition methods in early breast cancer prevention trials. Clin Can Res. Aug 15 2007; 13(16):4943-8. PMID 17699874

17. Bushnaq ZI, Ashfaq R, Leitch AM, et al. Patient variables that predict atypical cytology by nipple duct lavage. Cancer. Apr 1 2007; 109(7):1247-54. PMID 17326050

18. Visvanathan K, Santor D, Ali SZ, et al. The reliability of nipple aspirate and ductal lavage in women at increased risk for breast cancer -- a potential tool for breast cancer risk assessment and biomarker evaluation. Cancer Epidemiol Biomar Preven. May 2007; 16(5):950-5. PMID 17507621

19. Khan SA, Lankes HA, Patil DB, et al. Ductal lavage is an inefficient method of biomarker measurement in high-risk women. Cancer Prev Res – Philadelphia. Mar 2009; 2(3):265-73. PMID 19223577

20. ECRI Institute. Ductal lavage and nipple aspiration for identifying women at high risk of developing breast cancer. Plymouth Meeting (PA): ECRI Institute; 2014 Sep. 8 p. (Hotline Response).

21. NCCN - Breast Cancer Risk Reduction V.1.2017. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology ™. Available at <http://www.nccn.org> (accessed on February 23, 2017).

22. FDA – Safety Communication and Recall Notification for Nipple Aspirate Test. Food and Drug Administration – Center for Devices and Radiologic Health (2013 December 12). Available at <http://www.fda.gov> (accessed on March 4, 2014, reconfirmed on February 23, 2017).

23. Epithelial Cell Cytology in Breast Cancer Risk Assessment and High-Risk Patient Management (Ductal Lavage and Suction Collection Systems). Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2009 June) Medicine 2.01.45 (Archived).

24. Love SM, Barsky SH. Breast duct endoscopy to study stages of cancerous breast disease. Lancet. Oct 12 1996; 348(9033):997-9. PMID 8855857

25. Shen KW, Wu J, Lu JS, et al. Fiberoptic ductoscopy for patients with nipple discharge. Cancer. Oct 1 2000; 89(7):1512-9. PMID 11013365

26. Shen KW, Wu J, Lu JS, et al. Fiberoptic ductoscopy for breast cancer patients with nipple discharge. Surg Endo. Nov 2001; 15(11):1340-5. PMID 11727147

27. Dooley WC. Routine operative breast endoscopy during lumpectomy. Ann Surg Oncol. Jan-Feb 2003; 10(1):38-42. PMID 12513958

28. Dooley WC, Francescatti D, Clark L, et al. Office-based breast ductoscopy for diagnosis. Am J Surg. Oct 2004; 188(4):415-8. PMID 15474438

29. Sauter ER, Ehya H, Klein-Szanto AJ, et al. Fiberoptic ductoscopy findings in women with and without spontaneous nipple discharge. Cancer. Mar 1 2005; 103(5):914-21. PMID 15666326

30. Matsunaga T, Kawakami Y, Namba K, et al. Intraductal biopsy for diagnosis and treatment of intraductal lesions of the breast. Cancer. Nov 15 2004; 101(10):2164-9. PMID 15484220

31. Grunwald S, Bojahr B, Schwesinger G, et al. Mammary ductoscopy for the evaluation of nipple discharge and comparison with standard diagnostic techniques. J Minim Invas Gynecol. Sep-Oct 2006; 13(5):418-23. PMID 16962525

32. Al Sarakbi W, Salhab M, Mokbel K. Does mammary ductoscopy have a role in clinical practice? Int Sem Surg Oncol. 2006; 3:16. PMID 16808852

33. Sharma R, Dietz J, Wright H, et al. Comparative analysis of minimally invasive microductectomy versus major duct excision in patients with pathologic nipple discharge. Surgery. Oct 2005; 138(4):591-6; discussion 596-7. PMID 16269286

34. Louie LD, Crowe JP, Dawson AE, et al. Identification of breast cancer in patients with pathologic nipple discharge: does ductoscopy predict malignancy? Am J Surg. Oct 2006; 192(4):530-3. PMID 16978968

35. Hunerbein M, Dubowy A, Raubach M, et al. Gradient index ductoscopy and intraductal biopsy of intraductal breast lesions. Am J Surg. Oct 2007; 194(4):511-4. PMID 17826068

36. Grunwald S, Heyer H, Paepke S, et al. Diagnostic value of ductoscopy in the diagnosis of nipple discharge and intraductal proliferations in comparison to standard methods. Onkologie. May 2007; 30(5):243-8. PMID 17460418

37. Liu GY, Lu JS, Shen KW, et al. Fiberoptic ductoscopy combined with cytology testing in the patients of spontaneous nipple discharge. Breast Can Res Treat. Mar 2008; 108(2):271-7. PMID 17473979

38. Jacobs VR, Paepke S, Ohlinger R, et al. Breast ductoscopy: technical development from a diagnostic to an interventional procedure and its future perspective. Onkologie. Nov 2007; 30(11):545-9. PMID 17992024

39. NCCN - Breast Cancer Screening and Diagnosis V.1.2016. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology ™. Available at <http://www.nccn.org> (accessed on February 23, 2017).

40. Moncrief RM, Nayar R, Diaz LK, et al. A comparison of ductoscopy-guided and conventional surgical excision in women with spontaneous nipple discharge. Ann Surg. Apr 2005; 241(4):575-81. PMID 15798458

41. Sauter ER, Ehya H., Schlatter L, et al. Ductoscopic cytology to detect breast cancer. Cancer J. Jan-Feb 2004; 10(1):33-41; discussion 15-6. PMID 15000493

42. MammoView™ Breast Endoscopy System – Product information. Boston, Massachusetts: Solos Endoscopy, (2010). Available at <http://www.solos.com> (accessed on February 23, 2017).

43. Breast Duct Endoscopy (Archived). Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2008 July) Medicine 2.01.55.

44. Ichihara S, Ando M, Maksimenko A, et al. 3-D reconstruction and virtual ductoscopy of high-grade ductal carcinoma in situ of the breast with casting type calcifications using refraction-based X-ray CT. Virchows Arch. Jan 2008; 452(1):41-7. PMID 18000681

Policy History:

Date Reason
9/14/2019 Document became inactive.
5/15/2018 Reviewed. No changes.
4/15/2017 Document updated with literature review. Coverage unchanged.
4/15/2016 Reviewed. No changes.
1/1/2016 Document updated with literature review. Breast ductoscopy has been changed from being considered medically necessary to experimental, investigational and/or unproven when used in combination with cytology evaluation for patients who have nipple discharge without a palpable mass. Otherwise, coverage unchanged. Rationale significantly reorganized.
8/15/2014 Document updated with literature review. The following was added as a coverage change: Breast ductoscopy or “fiberoptic” ductoscopy combined with cytology evaluation may be considered medically necessary for patients who have nipple discharge without a palpable mass. The following was added to the indications for breast ductal lavage “breast cancer screening”. The following was added to the indications for breast ductoscopy “breast cancer screening or assessment of breast cancer risk”. Coverage unchanged for virtual ductoscopy.
1/1/2012 Document updated with literature review. Coverage unchanged. Title changed from Breast Ductal Lavage, Endoscopy, or Ductoscopy to Breast Ductal Lavage or Ductoscopy. This policy is no longer scheduled for routine literature review and update.
1/1/2009 Revised/updated entire document.
2/1/2006 Revised/updated entire document.
10/1/2002 New medical document.

Archived Document(s):

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