BlueCross and BlueShield of Montana Medical Policy/Codes
Breast Ductal Lavage or Ductoscopy
Chapter: Surgery: Procedures
Current Effective Date: September 24, 2013
Original Effective Date: September 24, 2013
Publish Date: June 24, 2013
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 (such as, 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 Saline is infused and ductal fluid withdrawn; and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.

The following table is a summary of the approved U.S. Food and Drug Administration (FDA) ductal lavage or suction devices and those in clinical trials which are currently being used.

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

Mammary Aspiration Specimen Cytology Test (MASCT)

December 2001 for  Marketing Device

Breast Aspirator

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

Breast Ductoscopy

Breast ductoscopy (mammary/breast duct endoscopy, fiberoptic ductoscopy or mammoscopy) 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.

The following table is a summary of the approved FDA devices and those in clinical trials.

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 reconstruction technique using computed tomography (CT) scans of the breast, is being investigated in clinical studies as another approach.

Policy

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.

Coverage

Blue Cross and Blue Shield of Montana (BCBSMT) considers breast ductal lavage of the mammary ducts --including suction collection-- to perform epithelial cell cytology on nipple aspirate fluid (NAF) for assessment of breast cancer risk and manage patients at high-risk of breast cancer experimental, investigational and unproven.

Breast ductoscopy or “fiberoptic” ductoscopy of the mammary ducts for diagnostic measures and/or therapeutic procedures are considered experimental, investigational and unproven.

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 unproven.

Rationale

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.  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 and colleagues reported on a multicenter clinical trial of 507 women who underwent ductal lavage.  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 and colleagues 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.  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. 

More recently Fabian and colleagues 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.  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.  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%).  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.  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.  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, 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. 
  • 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 are supported by a 2002 Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Center (TEC) Assessment that offered the following observations and conclusions:

  • No studies directly compare routine surveillance vs. 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 NSABBP 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.

2005 Update

In 2005, a review of the literature did not identify any articles that addressed the limitations in the literature discussed above. Therefore, the coverage statement is unchanged.  Khan and colleagues published a study of 32 women who underwent ductal lavage in 44 breasts with known cancer prior to mastectomy.  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.  Brogi and colleagues report 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.

A variety of review articles and commentaries have also been published that discuss potential applications of ductal lavage.  Both of the Khan and Brogi articles cite the same studies as discussed in the 2002 BCBSA TEC Assessment; however, to date, there are no controlled trials that formally investigate the proposed applications of ductal lavage.  Currently, two clinical trials are ongoing.  In a multi-institutional study sponsored by Cytyc, women at increased risk for breast cancer will undergo ductal lavage of fluid-producing ducts every six months for three years.  The end point is association of ductal lavage cytologic results with development of breast cancer.  The National Cancer Institute (NCI) has sponsored a multi-institution study in which results of random periareolar FNA with be compared with ductal lavage in high-risk premenopausal women before and after twelve-months of treatment with celecoxib.

In 2003, the American Society of Breast Surgeons issued an “official statement” regarding ductal lavage, which reads in part, “Ductal lavage is a minimally invasive method of collecting breast epithelial cells for cytological examination.  Because most breast cancer originates from the same layer of epithelial cells that line the milk ducts, it appears that atypical changes in breast epithelial cells will confer similar relative risk increases regardless of the method of collection.  There is no reason to believe that the long-term risk associated with atypia diagnosed by ductal lavage will be different from other methods of determining cytologic atypia.

The American Society of Breast Surgeons supports the use of ductal lavage as a cell-based risk assessment tool in high-risk and borderline-risk women to assist them in making more informed decisions regarding risk reduction and management options.  This information can help to guide consideration of a variety of management options ranging from risk reduction therapy (tamoxifen or enrollment in the STAR trial) to closer surveillance or even prophylactic mastectomy….Long-term studies are necessary to better define the risk assessment contribution of cytologic atypia detected via these and other methods.  The American Society of Breast Surgeon encourages participation in such trials.”

2008 Update

A MedLine database search was performed for the period of 2006 through August 2008.  None of the publications found identified would prompt a change in the coverage statement.  In particular, no results have been published from controlled trials that investigate the proposed applications of ductal lavage.  One article raised questions that low interrater cytologic consistency may compromise the interpretation of clinical studies of ductal lavage.

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.  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 compare breast tissue acquisition by ductal lavage with random periareolar FNA (immediately following aspiration) in 86 women at high-risk for breast cancer.  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.  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.

A number of recent studies suggest poor technical and diagnostic performance of ductal lavage.  This technology has not been shown to improve the new health outcome.  Therefore, the coverage position remains unchanged. 

2011 Update

A search of peer reviewed literature through August 2011 identified no new high-quality clinical trial publications or any additional information that would change the coverage position of this medical policy.

Visvanathan et al. 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. 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.”

In January 2011, National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology breast cancer screening and diagnosis guidelines stated that current evidence does not support the routine use of ductal lavage as a screening procedure.

In July 2011, the NCI’s Physician Data Query (PDQ®) maintains their investigational position on the following breast cancer screening modalities, FNA, NAF, and ductal lavage. 

Summary

The available literature regarding ductal lavage and suction collection systems for breast cancer risk assessment are inadequate to draw clinical conclusions.  The coverage statement remains unchanged.  These procedures are experimental, investigational and 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 has 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.  Ductoscopy is currently being used in research and clinical trial collaborations to demonstrate the value of this technology in the detection and management of early stage breast cancer and other forms of intraductal breast disease.  Therefore, the safety and effectiveness of ductoscopy has not been established and is considered experimental, investigational and unproven.

2005 Update

In 2005, a review 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.  The authors concluded the intraductal approach is feasible for the study of the early changes of breast cancer.  Shen and colleagues studied the role of ductoscopy in 259 women with nipple discharge.  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.  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.  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.  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, Matsunage and colleagues have also documented the technical feasibility of ductoscopy in large a case series of patients with nipple discharge.

In summary, the available published data consist of uncontrolled case series.  The data are insufficient to permit scientific conclusion regarding the role of ductoscopy in the evaluation and management of patients with known or suspected breast cancer.

2008 Update

A MedLine database search was performed for the period of 2006 through August 2008.  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.  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.  The NCCN does not currently include ductoscopy in their recommendations for diagnostic follow-up of pathological nipple discharge.  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.  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.  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 and colleagues compared various diagnostic tests in patients with breast disease.  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 cancer 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 are 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.  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. 

The 2008 NCCN guidelines for evaluation of those with nipple discharge again do not recommend breast duct endoscopy.  In another paper from a European center, Jacobs describes ongoing research and development in an attempt to have breast endoscopy become a potential therapeutic as well as a diagnostic approach.  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.  The coverage position is unchanged; this procedure is considered experimental, investigational and unproven because its impact on health outcomes is uncertain.

2011 Update

A search of peer reviewed literature through August 2011 identified no new clinical trial publications or any additional information that would change the coverage position of this medical policy.

Virtual Ductoscopy

A MedLine database search was performed through August 2008.  The data are insufficient to permit scientific conclusion regarding the role of virtual ductoscopy in the evaluation and management of patients with known or suspected breast cancer.  Therefore, this procedure is considered experimental, investigational and unproven because its impact on health outcomes is uncertain.

2011 Update

A search of peer reviewed literature through August 2011 identified no new clinical trial publications or any additional information that would change the coverage position of this medical policy.

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. 

ICD-9 Codes

174.0, 610.4, 611.79, V10.3, V16.3, V76.10, V76.19

ICD-10 Codes

C50.011, C50.012, C50.019, N60.41, N60.42, N60.49, N64.52, N64.59, Z12.39, Z80.3, Z85.3

Procedural Codes: 19499
References

Breast Ductal Lavage or Suction Collection 

  1. Dupont, W.D. and D.L. Page.  Risk factors for breast cancer in women with proliferative breast disease.  New England Journal of Medicine (1985 January 17) 312(3):146-51.
  2. Wrensch, M.R., Petrakis, N.L., et al.  Breast cancer incidence in women with abnormal cytology in nipple aspirates of breast fluid.  American Journal of Epidemiology (1992 January 15) 135(2):130-41.
  3. Fisher, B., Costantino, J.P., et al.  Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study.  Journal of the National Cancer Institute (1998 September 16) 90(18):1371-88.
  4. Fabian, C.J., Kimler, B.F., et al.  Short-term breast cancer prediction by random periareolar fine-needle aspiration cytology and the Gail risk model.  Journal of the National Cancer Institute (2000 August 2) 92(15):1217-27.
  5. Port, E.R., Montgomery, L.L., et al.  Patient reluctance toward tamoxifen use for breast cancer primary prevention.  Annals of Surgical Oncology (2001 August) 8(7):580-5.
  6. Dooley, W.C., Ljung, B.M., et al.  Ductal lavage for detection of cellular atypia in women at high-risk for breast cancer.  Journal of the National Cancer Institute (2001 November 7) 93(21):1624-32.
  7. Wrensch, M.R., Petrakis, N.L., et al.  Breast cancer risk in women with abnormal cytology in nipple aspirates of breast fluid.  Journal of the National Cancer Institute (2001 December 5) 93(23):1791-8.
  8. 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.
  9. Wright, T., and A. McGechan.  Breast cancer: new technologies for risk assessment and diagnosis.  Molecular Diagnostics (2003) 7(1):49-55.
  10. BreastSurgeons.org – Ductal Lavage and Cell-Based Risk Assessment (2003 April 30).  The American Society of Breast Surgeons Official Statement.  Available at http://www.breastsurgeons.org (accessed on 2005 September 20).
  11. O’Shaughnessy, J.A.  Ductal lavage: Clinical utility and future promise.  Surgical Clinics of North America (2003 August) 83(4):753-69.
  12. Brogi, E., Robson, M., et al.  Ductal lavage in patients undergoing mastectomy for mammary carcinoma: A correlative study.  Cancer (2003 November 15) 98(10):2170-6.
  13. Newman, L.A.  Ductal lavage: What we know and what we don’t.  Oncology (2004 February) 18(2):179-85; discussion 185-6, 189, 192.
  14. Fabian, C.J., Kimler, B.F., et al.  Ductal lavage for early detection – what doesn’t come out in the wash.  Journal of the National Cancer Institute (2004 October 20) 96(20):1488-9.
  15. Khan, S.A., Wiley, E.L., et al. Ductal lavage findings in women with known breast cancer undergoing mastectomy.  Journal of the National Cancer Institute (2004 October 20) 96(20):1510-7.
  16. Proctor, K.A.S., Rowe, L.R., et al.  Cytologic features of nipple aspirate fluid using an automated invasive collection device: a prospective observational study.  BMC Womens Health (2005) 5:10.
  17. Johnson-Maddux, A., Ashfaq, R., et al.  Reproducibility of cytologic atypia in repeat nipple duct lavage.  Cancer (2005 March 15):1129-36.
  18. Khan, S.A., Wolfman, J.A., et al.  Ductal lavage findings in women with mammographic microcalcifications undergoing biopsy.  Annals of Surgical Oncology (2005 September) 12(9):689-96.
  19. ClinicalTrials.gov – Breast Duct Lavage and Breast Duct Endoscopy for Detecting Breast Cancer (2005 August 26).  U.S. National Institutes of Health and National Cancer Institute Clinical Trial Summary.  Available at http://www.clinicaltrials.gov (accessed on 2005 September 16).
  20. FirstCyte Breast Test – Product information. Marlborough, Maryland: Cytyc Corporation (1997-2005).  Available at http://www.cytyc.com (accessed on 2005 September 20).
  21. Ductal Lavage – Product information. Greenville, South Carolina: Imaginis Corporation (1997-2005).  Available at http://www.imaginis.com (accessed on 2005 September 16).
  22. Visvanathan, K., Santor, D., et al.  The importance of cytologic intrarater and interrater reproducibility: the case of ductal lavage.  Cancer Epidemiology, Biomarkers and Prevention (2006 December) 15(12):2553-6.
  23. Bushnaq, Z.I., Ashfaq, R., et al.  Patient variables that predict atypical cytology by nipple duct lavage.  Cancer (2007 April 1) 109(7):1247-54.
  24. Visvanathan, K., Santor, D., 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 Epidemiology, Biomarkers and Prevention (2007 May) 16(5):950-5.
  25. ASBS – Ductal Cell-Based Risk Assessment (2007 May 6).  Columbia, Maryland: The American Society of Breast Surgeons, Board of Directors.  Available at http://www.breastsurgeons.org (accessed on 2008 August 15).
  26. Arun, B., Valero, V., et al.  Comparison of ductal lavage and random periareolar fine needle aspiration as tissue acquisition methods in early breast cancer prevention trials.  Clinical Cancer Research (2007 August 15) 13(16):4943-8.
  27. Hoda, R.S.  Non-gynecologic cytology on liquid-based preparations: a morphologic review of facts and artifacts.  Diagnostic Cytopathology (2007 October) 35(10):621-34.
  28. Papillo, J.L., St. John, T.L., et al.  Effectiveness of the ThinPrep Imaging System: clinical experience in a low-risk screening population.  Diagnostic Cytopathology (2008 March) 36(3):155-60.
  29. Patil, D.B., Lankes, H.A., et al.  Reproducibility of ductal lavage cytology and cellularity over a six month interval in high risk women.  Breast Cancer Research and Treatment (2008 November) 112(2):327-33.
  30. Khan, S.A., Lankes, H.A., et al.  Ductal lavage is an inefficient method of biomarker measurement in high-risk women.  Cancer Prevention and Research – Philadelphia (2009 March) 2(3):265-73.
  31. 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).
  32. Wood, M.E., Stanley, M.A., et al.  Ductal lavage of cancerous and unaffected breasts: procedures success rate and cancer detection.  ACTA Cytologica (2009 July-August) 53(4):410-5.
  33. NCI PDQ – Breast Cancer Screening Modalities (2011 July 27).  National Cancer Institute Physicians Data Query.  Available at http://www.cancer.gov> (accessed on 2011 September 12).
  34. NCCN.org – Breast Cancer Screening and Diagnosis Guidelines (2011 January) V.I.2011:1-50.  National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology ™.  Available at http://www.nccn.org (accessed on 2011 September 12).

Breast Ductoscopy

  1. Heywang-Kobrunner, S.H.  Nonmammographic breast imaging techniques.  Current Opinion in Radiology (1992 October) 4(5):146-54.
  2. Love, S.M. and S.H. Barsky.  Breast duct endoscopy to study stages of cancerous breast disease. Lancet (1996 October 12) 348(9033):997-9.
  3. Shen, K.W., Wu, J., et al.  Fiberoptic ductoscopy for patients with nipple discharge.  Cancer (2000 October 1) 89(7):1512-9.
  4. Shen, K.W., Wu, J., et al.  Fiberoptic ductoscopy for breast cancer patients with nipple discharge. Surgical Endoscopy (2001 November) 15(11): 1340-5.
  5. Dooley, W.C.  Routine operative breast endoscopy during lumpectomy.  Annals of Surgical Oncology (2003 January – February) 10(1):38-42.
  6. Breast Endoscopy – Product information.  Palo Alto, California: Acueity, Inc., (2004). 
  7. Available at http://www.acueity.com (accessed on 2005 September 21).
  8. Sauter, E.R., Ehya, H., et al.  Ductoscopic cytology to detect breast cancer.  Cancer Journal (2004 January – February) 10(1):33-41; discussion 15-6.
  9. Dooley, W.C., Francescatti, D., et al.  Office-based breast ductoscopy for diagnosis.  American Journal of Surgery (2004 October) 188(4):415-8.
  10. Matsunaga, T., Kawakami, Y., et al.  Intraductal biopsy for diagnosis and treatment of intraductal lesions of the breast.  Cancer (2004 November 15) 101(10):2164-9.
  11. Breast Duct Endoscopy. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2005 January) Medicine 2.01.55.
  12. Sauter, E.R., Ehya, H., et al.  Fiberoptic ductoscopy findings in women with and without spontaneous nipple discharge.  Cancer (2005 March 1) 103(5):914-21.
  13. Moncrief, R.M., Nayar, R., et al.  A comparison of ductoscopy-guided and conventional surgical excision in women with spontaneous nipple discharge.  Annals of Surgery (2005 April) 241(4):575-81.
  14. ClinicalTrials.gov – Duct Endoscopy in Assessing Cellular Atypia in the Breast Duct Fluid of Women With a Genetic Risk for Breast Cancer (2005 September 9).  U.S. National Institutes of Health and National Cancer Institute Clinical Trial Summary.  Available at http://www.clinicaltrials.gov (accessed on 2005 September 16).
  15. Sharma, R., Dietz, J., et al.  Comparative analysis of minimally invasive microductectomy versus major duct excision in patients with pathologic nipple discharge.  Surgery (2005 October) 138(4):591-6; discussion 596-7.
  16. Al Sarakbi, W., Salhab, M., et al.  Does mammary ductoscopy have a role in clinical practice?  International Seminars in Surgical Oncology (2006) 3:16.
  17. Grunwald, S., Bojahr, B., et al.  Mammary ductoscopy for the evaluation of nipple discharge and comparison with standard diagnostic techniques.  Journal of Minimally Invasive Gynecology (2006 September-October) 13(5):418-23.
  18. Louie, L.D., Crowe, J.P., et al.  Identification of breast cancer in patients with pathologic nipple discharge: does ductoscopy predict malignancy?  American Journal of Surgery (2006 October) 192(4):530-3.
  19. Grunwald, S., Heyer, H., et al.  Diagnostic value of ductoscopy in the diagnosis of nipple discharge and intraductal proliferations in comparison to standard methods.  Onkologie (2007 May) 30(5):243-8.
  20. Hunerbein, M., Dubowy, A., et al.  Gradient index ductoscopy and intraductal biopsy of intraductal breast lesions.  American Journal of Surgery (2007 October) 194(4):511-4.
  21. Jacobs, V.R., Paepke, S., et al.  Breast ductoscopy: technical development from a diagnostic to an interventional procedure and its future perspective.  Onkologie (2007 November) 30(11):545-9.
  22. Liu, G.Y., Lu, J.S., et al.  Fiberoptic ductoscopy combined with cytology testing in the patients of spontaneous nipple discharge.  Breast Cancer Research and Treatment (2008 March) 108(2):271-7.
  23. Breast Duct Endoscopy.  Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2008 July) Medicine 2.01.55 (Archived).
  24. Kamali, S., Bender, O., et al.  Ductoscopy in the evaluation and management of nipple discharge. Annals of Surgical Oncology (2010 March) 17(3):778-83.
  25. Sauter, E.R., Klein-Szanto, A., et al.  Nipple aspirate fluid and ductoscopy to detect breast cancer.  Diagnostic Dytopathology (2010 April) 38(4):244-51.
  26. NCCN.org – Breast Cancer Screening and Diagnosis Guidelines (2011 January) V.I.2011:1-50.  National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology ™.  Available at http://www.nccn.org (accessed on 2011 September 12).
  27. Dubowy, A., Raubach, M., et al.  Breast ductoscopy; ductoscopy from a diagnostic to an interventional procedure and its future perspective.  ACTA Chirurgica Belgica (2011 May-June) 111(3):124-5.

Virtual Ductoscopy

  1. Heywang-Kobrunner, S.H.  Nonmammographic breast imaging techniques.  Current Opinion in Radiology (1992 October) 4(5):146-54.
  2. Ichihara, S., Ando, M., 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 Archives (2008 January) 452(1):41-7.
History
June 2013  New 2013 BCBSMT medical policy.  Considered experimental, investigational and unproven. 
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Breast Ductal Lavage or Ductoscopy