Ductal Lavage and Fiberoptic Ductoscopy for Cancer Screening

Clinical & Quality Management MEDICAL POLICY

DUCTAL LAVAGE AND FIBEROPTIC DUCTOSCOPY FOR CANCER SCREENING

Policy Number: 2015M0096A Effective Date: December 1, 2015

Table of Contents: Page: Cross Reference Policy:

POLICY DESCRIPTION 2 Breast Reconstructive Surgery, COVERAGE RATIONALE/CLINICAL CONSIDERATIONS 2 2013M0043A BACKGROUND 2 REGULATORY STATUS 3 Genetic Testing, 2015M0038B CLINICAL EVIDENCE 4 APPLICABLE CODES 5 Genetic Expression Assays for Breast Tumor Tissue Oncotype DX®/ REFERENCES 6 MammaPrint®, 2014M0008B POLICY HISTORY/REVISION INFORMATION 7

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Clinical & Quality Management MEDICAL POLICY

POLICY DESCRIPTION:

This policy discusses ductal lavage and fiberoptic ductoscopy, two methods of collecting breast fluid. The obtained fluids undergo cytological examination of the ductal epithelial cells to assist in assessing the patient’s risk for breast cancer. These procedures are intended to be used in conjunction with clinical breast examination and mammography for the early detection and pathological diagnosis of nonpalpable breast cancers and precancerous lesions in high-risk women with normal or indeterminate findings by radiological and physical examination. Examination of nipple aspirate fluid is sometimes called the “breast pap smear.”

COVERAGE RATIONALE / CLINICAL CONSIDERATIONS:

Breast ductal lavage is considered UNPROVEN AND NOT MEDICALLY NECESSARY for the use of breast cancer screening of either low-risk or high-risk women due to insufficient published clinical evidence in peer-reviewed medical literature demonstrating the safety and/or impact on health outcomes or patient management. Fiberoptic ductoscopy, with or without ductal lavage, is considered UNPROVEN AND NOT MEDICALLY NECESSARY due to insufficient published clinical evidence in peer-reviewed medical literature demonstrating the safety and/or impact on health outcomes or patient management. The HALO® Breast Pap Test is considered UNPROVEN AND NOT MEDICALLY NECESSARY for use in breast cancer screening of either low-risk or high-risk women due to insufficient published clinical evidence in peer-reviewed medical literature demonstrating the safety and/or impact on health outcomes or patient management.

Clinical Considerations: The FDA states a nipple aspirate fluid test is not a replacement for mammography, other breast imaging tests, or breast biopsy, and should not be used alone to screen for or diagnose breast cancer.

BACKGROUND:

Some breast cancers are believed to arise from a series of progressive cytogenetic and histopathological changes that are reflected by transformation of normal tissue to mild hyperplasia, moderate hyperplasia, and atypical hyperplasia followed by carcinoma in situ (CIS) and invasive cancer. Breast cancer risk increases by 1.5 to 2 times in the presence of proliferative breast disease without atypia or usual hyperplasia, and by 4 to 5 times with a biopsy history of atypical hyperplasia. However, it remains unclear whether a cytological diagnosis of atypia correlates directly with a subsequent histopathological diagnosis of atypical hyperplasia or breast cancer. Breast biopsies, open surgical excision, or excision of the duct are performed when a palpable lump, mammographic abnormality, or bloody nipple discharge is found. It has been hypothesized that identification of breast cancer at an early, preclinical phase might allow for earlier treatment and an improved prognosis. Noninvasive methods for collecting and analyzing epithelial cells and other biomarkers of early breast cancer in fluid specimens obtained from the ducts of the breast

Clinical & Quality Management MEDICAL POLICY

have been evaluated. Studies have shown that breast cancer risk is increased when atypical hyperplasia is found in nipple aspirate fluid (NAF) specimens, and following a diagnosis of atypical hyperplasia by periareolar fine-needle aspiration (FNA) cytology. However, nipple aspiration has limited utility for diagnosis since inadequate NAF specimens are collected in up to 50% of women. Breast ductal lavage (DL) and fiberoptic ductoscopy (FDS) are used to evaluate patients at risk for breast cancer. These procedures are intended to be used in conjunction with clinical breast examination and mammography for the early detection and pathological diagnosis of nonpalpable breast cancers and precancerous lesions in high-risk women with normal or indeterminate findings by radiological and physical examination. Breast DL is an invasive technique for the collection of breast ductal epithelial cells for cytological analysis. A microcatheter is inserted into each NAF-producing duct, local anesthetic is infused, and saline is introduced to wash out the ductal contents, which are analyzed cytopathologically. DL is intended to be used in high-risk women with normal findings on clinical breast examination (CBE) and mammography for the early detection of nonpalpable breast cancers and precancerous lesions. The purpose is to provide information for risk stratification. Fiberoptic ductoscopy (FDS), the direct visualization of the breast duct lining using a very thin fiberoptic scope, has been employed to identify the source of atypical cells found on DL, as well as for evaluation of abnormal nipple discharge in conjunction with aspiration cytology, biopsy, or surgical excision. FDS systems have microendoscopes with an outer air channel on the fiberscope, which permits instillation and re- collection of saline to retrieve cells from the breast ductal system. Nipple aspiration can also be done noninvasively, using the HALO Breast Pap Test system. HALO is an automated system that collects nipple aspirate fluid (NAF) using a combination of heat, massage and suction.

REGULATORY STATUS:

1. U.S. FOOD AND DRUG ADMINISTRATION (FDA): Devices for collecting ductal fluid can be found at the following website using product code KNW. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm. Accessed Oct 1, 2015. The HALO® Breast Pap Test (HALO Healthcare) was approved for marketing by the FDA on September 23, 2002. The device is intended to non-invasively extract samples of breast duct fluid for breast cancer screening, providing a sample for a "Pap smear" for the breast. Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf2/K020848.pdf. Accessed Oct 1, 2015. On December 12, 2013, the FDA issued a Safety Alert regarding nipple aspirate testing. The alert states 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. The FDA is not aware of any valid scientific data to show that a nipple aspirate test by itself is an effective screening tool for any medical condition including the early detection of breast cancer or other breast disease. Certain manufactures are promoting the use of nipple aspirate tests as a stand-alone evaluation tool for screening and diagnosing breast cancer, claiming they are an alternative to biopsy or mammography. They also claim that a nipple aspirate test can detect pre-cancerous abnormalities and

Clinical & Quality Management MEDICAL POLICY

diagnose breast cancer before mammography with just a sample of a few cells. The FDA is concerned that women will believe these misleading claims about a nipple aspirate test and not get mammograms and/or other needed breast imaging tests or biopsies. This may lead to serious adverse health consequences. Possible health consequences include false negative test results, indicating the absence of breast cancer when cancer exists, and false positive test results, indicating the presence of breast cancer when none exists. False negative results may lead to delayed diagnosis and/or delayed treatment of breast cancer, with increased risk of serious illness or death. False positive results may lead to needless patient anxiety, along with unnecessary additional testing and treatment. Information is available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/uc m378489.htm. Accessed: Oct 1, 2015. 2. CENTERS FOR MEDICARE AND MEDICAID SERVICES (CMS): CMS has not established a specific National Coverage Determination (NCD) that addresses ductal lavage, fiberoptic ductoscopy or nipple aspirate fluid. Local Coverage Determinations (LCDs) do not exist for ductal lavage, fiberoptic ductoscopy or nipple aspirate fluid. 3. MINNESOTA DEPARTMENT OF HUMAN SERVICES (DHS): Minnesota DHS does not have a policy statement regarding ductal lavage, fiberoptic ductoscopy or nipple aspirate in its Provider Manual.

CLINICAL EVIDENCE:

Breast ductal lavage (DL) is intended for the cytological analysis of breast ductal epithelial cells of women who are at high risk for breast cancer but who have negative findings on mammography and CBE to facilitate the early diagnosis of breast cancer or precancer and to provide information for risk stratification. The technique is used in conjunction with standard methods of surveillance such as CBE, mammography, and ultrasonography as a tool for early detection. If DL detects atypical cells, a high-risk patient could receive treatment aimed at reducing the risk of invasive breast cancer development. Risk-reduction strategies include chemoprevention with agents such as tamoxifen or raloxifene, and prophylactic mastectomy, the surgical removal of the breasts. While neither method can absolutely prevent the disease, each has been shown to reduce the risk of breast cancer in some women.

The feasibility of fiberoptic ductoscopy (FDS) was first demonstrated in a study published in 1996 that involved 9 patients scheduled to undergo mastectomy who first underwent breast duct endoscopy. FDS, the direct visualization of the breast duct lining using a very thin fiberoptic scope after intraductal cannulation, has been employed to identify the source of atypical cells found on DL. It also allows for evaluation of abnormal nipple discharge in conjunction with aspiration cytology, biopsy, or surgical excision, and has been used as an intraoperative tool to guide breast surgery. FDS systems have microendoscopes (0.9 mm in diameter) with an outer air channel on the fiberscope, which permits instillation and re-collection of saline to retrieve cells from the breast ductal system (Love and Barsky, 1996; Dooley et al., 2001; Dooley, 2002; Morrow et al., 2002; Dooley, 2003; O’Shaughnessy, 2003; Badve, 2004; Cytyc Corp., 2004a; Cytyc Corp., 2004b; Locke et al., 2004).

Clinical & Quality Management MEDICAL POLICY

SUMMARY: Evidence suggests that ductal lavage can confirm atypical cells in women at high risk for breast cancer due to a personal or strong family history of breast cancer, who have a Gail index score of ≥ 1.7, and/or who carry a BRCA1 or BRCA2 mutation. However, there is a paucity of evidence on the impact of DL on patient management and health outcomes. There is no information on the efficacy and safety of DL in the following subgroups: women at average risk for breast cancer or women with abnormal findings on clinical breast examination and/or mammography; or for women with prior irradiation or surgery on the breast to be lavaged or women receiving chemotherapy. The introduction of the Halo Breast Pap Test has been compared to the introduction of the cervical pap test in the 1950s, which has been credited with lowering cervical cancer mortality by more than 70 % through the identification of abnormal cells in the cervix. However, whether the same can be said for the Halo Breast Pap Test remains to be seen. The clinical value of the Halo Breast Pap Test system has yet to be established by further prospective, randomized controlled studies.

Evidence suggests that fiberoptic ductoscopy is feasible, that it yields clinical information on intraductal disease and that it allows for the performance and cytological examination of DL washings for detection of atypical cells. However, there is minimal evidence on how this technique would be used in the management of the patient, i.e., either in determining the need for other diagnostic tests, such as mammography or ductography, in assessing the need for surgical biopsy or excision, or in planning the extent of surgical excision.

APPLICABLE CODES:

The Current Procedural Terminology (CPT®) codes and HCPCS codes listed in this policy are for reference purposes only. Listing of a service or device code in this policy does not imply that the service described by this code is a covered or non-covered health service. The inclusion of a code does not imply any right to reimbursement or guarantee claims payment. Other medical policies and coverage determination guidelines may apply. HCPCS Codes Description C8903 Magnetic resonance imaging with contrast, breast; unilateral C8904 Magnetic resonance imaging without contrast, breast; unilateral ICD-9 Codes Description 174.0 - 175.9 Malignant neoplasm of breast [covered for known breast intraductal cancer when fiberoptic ductoscopy is used as a guide for resection only] 611.0 Inflammatory disease of breast 611.5 – 611.9 Galactocele, galactorrhea not associated with childbirth, signs and symptoms in breast, or other specified and unspecified breast disorders 611.79 Other disorders of breast [nonlactational sporadic nipple discharge] ICD-10 Codes Description C50.011 - C50.929 Malignant neoplasm of breast [covered for known breast intraductal cancer when fiberoptic ductoscopy is used as a guide for resection only] N64.52 Nipple discharge [nonlactational sporadic nipple discharge] N61 Inflammatory disorders of breast N63 Other disorders of breast

Clinical & Quality Management MEDICAL POLICY

N64.3 - N64.51 N64.53 - N64.9 Z12.39 Encounter for other screening for malignant neoplasm of breast Z80.3 Family history of malignant neoplasm of breast Z85.3 Personal history of malignant neoplasm of breast CPT® Codes Description 19030 Injection procedure only for mammary ductogram or galactogram 19499* Unlisted procedure, breast 77053 Mammary ductogram or galactogram, single duct, radiological supervision and interpretation 77054 Mammary ductogram or galactogram, multiple ducts, radiological supervision and interpretation 88112 Cytopathology, selective cellular enhancement technique with interpretation (e.g., liquid based slide preparation method), except cervical or vaginal 88161 Cytopathology smears, any other source; preparation, screening and interpretation CPT® is a registered trademark of the American Medical Association.

REFERENCES:

1. Aetna. Policy Number 0517. Breast Ductal Lavage and Fiberoptic Ductoscopy. Last review 08/26/2014. Available at: https://www.aetna.com/health-care-professionals/clinical-policy-bulletins/medical-clinical-policy- bulletins.html#. Accessed Oct 22, 2015. 2. Badve S. Ductal lavage and its histopathologic basis: a cautionary tale. Diagn Cytopathol. 2004;30(3):166-171. 3. Badve S, Wiley E, Rodriguez N. Assessment of utility of ductal lavage and ductoscopy in breast cancer-a retrospective analysis of mastectomy specimens. Mod Pathol. 2003;16(3):206-209. 4. Brogi E, Robson M, Panageas KS, et al. Ductal lavage in patients undergoing mastectomy for mammary carcinoma: a correlative study. Cancer. 2003;98(10):2170-2176. 5. Carruthers CD, Chapleskie LA, Flynn MB, Frazier TG. The use of ductal lavage as a screening tool in women at high risk for developing breast carcinoma. Am J Surg. 2007;194(4):463-466. 6. Cytyc Corp. [Web site]. Information for Medical Professionals. Risk Assessment. 2004a. Available at: http://www.cytychealth.com/. Accessed Oct 22, 2015. 7. Dooley WC, Ljung BM, Veronesi U, et al. Ductal lavage for detection of cellular atypia in women at high risk for breast cancer. J Natl Cancer Inst. 2001;93(21):1624-1632. 8. Dooley WC. Routine operative breast endoscopy for bloody nipple discharge. Ann Surg Oncol. 2002;9(9):920-923. 9. Dooley WC. Ductal lavage, nipple aspiration, and ductoscopy for breast cancer diagnosis. Curr Oncol Rep.2003;5(1):63-65. 10. Evron E, Dooley WC, Umbricht CB, et al. Detection of breast cancer cells in ductal lavage fluid by methylation- specific PCR. Lancet. 2001;357(9265):1335-1336. 11. Halo Healthcare, Inc. HALO Breast Cytological Evaluation Test Overview. Available at: http://www.halohc.com/. Accessed Oct 22, 2015. 12. Hartman AR, Daniel BL, Kurian AW, et al. Breast magnetic resonance image screening and ductal lavage in women at high genetic risk for breast carcinoma. Cancer. 2004;100(3):479-489. 13. Hayes, Winifred S. Medical Technology Directory. Breast Ductal Lavage and Fiberoptic Ductoscopy for Breast Cancer Diagnosis and Screening. Published Aug 23, 2004. Reviewed: Dec 2,2008. Available at: https://www.hayesinc.com/subscribers/displayLogin.do. Accessed Oct 22, 2015. 14. Hünerbein M, Estévez Schwartz L, Schneider U, Schlag PM. Evaluation of pathologic nipple discharge with ductoscopy. J Am Coll Surg. 2003;197(4):697-698. 15. Khan SA, Wiley EL, Rodriguez N, et al. Ductal lavage findings in women with known breast cancer undergoing

Clinical & Quality Management MEDICAL POLICY

mastectomy. J Natl Cancer Inst. 2004;96(20):1510-1517. 16. King BL, Tsai SC, Gryga ME, et al. Detection of chromosomal instability in paired breast surgery and ductal lavage specimens by interphase fluorescence in situ hybridization. Clin Cancer Res. 2003;9(4):1509-1516. 17. Liu GY, Lu JS, Shen KW, et al. Fiberoptic ductoscopy combined with cytology testing in the patients of spontaneous nipple discharge. Breast Cancer Res Treat. 2008;108(2):271-277. 18. Locke I, Mitchell G, Eeles R. Ductal approaches to assessment and management of women at high risk for developing breast cancer. Breast Cancer Res. 2004;6(2):75-81. 19. Love SM, Barsky SH. Breast-duct endoscopy to study stages of cancerous breast disease. Lancet. 1996;348(9033):997-999. 20. Morrow M, Vogel V, Ljung BM, O’Shaughnessy JA. Evaluation and management of the woman with an abnormal ductal lavage. J Am Coll Surg. 2002;194(5):648-656. 21. National Comprehensive Cancer Network (NCCN). Guidelines Version 1.2015. Breast Cancer Screening and Diagnosis. Available: http://www.nccn.org/. Accessed Oct 22, 2015. 22. Proctor K, Rowe L, Bentz J. Cytologic features of nipple aspirate fluid using an automated non-invasive collection device: a prospective observational study, BMC Women's Health 2005, 5:10. 23. O’Shaughnessy JA. Ductal lavage: clinical utility and future promise. Surg Clin North Am. 2003;83(4):753-769, vii. 24. Shen KW, Wu J, Lu JS, et al. Fiberoptic ductoscopy for breast cancer patients with nipple discharge. Surg Endosc. 2001;15(11):1340-1345. 25. Yamamoto D, Shoji T, Kawanishi H, et al. A utility of ductography and fiberoptic ductoscopy for patients with nipple discharge. Breast Cancer Res Treat. 2001;70(2):103-108. 26. Yamamoto D, Senzaki H, Nakagawa H, et al. Detection of chromosomal aneusomy by fluorescence in situ hybridization for patients with nipple discharge. Cancer. 2003;97(3):690-694.

POLICY HISTORY: DATE ACTION/DESCRIPTION 10/12/2015 New Policy 2015M00xxA reviewed by Medical Policy Committee. 10/22/2015 Reviewed and approved by the Quality Improvement Advisory and Credentialing Council (QIACC). 11/01/2015 Published to UCare.org.

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