ADVANCES IN BREAST CANCER DIAGNOSIS AND TREATMENT: ESSENTIALS

Advances in breast cancer diagnosis and treatment Essentials_kapak

MANAGEMENT OF OCCULT BREAST CANCER

Berk Göktepe1 Levent Yeniay2

1Ege University, Faculty of Medicine, Department of General Surgery, İzmir, Türkiye
2Ege University, Faculty of Medicine, Department of General Surgery, İzmir, Türkiye

Göktepe B, Yeniay L. Management of Occult Breast Cancer. In: Citgez B editor. Advances in Breast Cancer Diagnosis and Treatment Essentials. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.157-164.

ABSTRACT

The definition of occult breast cancer (OBC) dates back to the 18th century. Cases classified as T0N+Mx are those in which no primary lesion can be identified in the breast using currently available imaging modalities, yet at least one axillary lymph node with pathological features suggestive of breast carcinoma metastasis is present. Today, the treatment of OBC remains controversial. The two most debated issues are whether the breast can be preserved and how to approach the axilla after neoadjuvant therapy. In this article, we aimed to review the current approaches to OBC in light of recent studies.

Over the past decades, advances in imaging such as breast MRI, tomosynthesis, and PET/CT have significantly improved the detection of otherwise hidden lesions, leading to refinements in diagnosis and staging. Despite these technological developments, a subset of patients continues to present with axillary metastases and no identifiable primary lesion, highlighting the unique clinical challenge posed by this disease entity. The rarity of OBC, with an incidence estimated between 0.1% and 3% of all breast cancers, further complicates the establishment of standardized management strategies.

Current evidence suggests that both mastectomy and whole-breast radiotherapy can provide effective locoregional control, with no clear consensus on superiority. Similarly, the role of axillary management has evolved, with sentinel lymph node biopsy and targeted axillary dissection increasingly considered in selected patients, particularly those responding well to neoadjuvant systemic therapy. Systemic therapy choices are generally guided by the molecular profile of the disease, emphasizing the importance of immunohistochemistry in diagnosis.

Future perspectives emphasize the integration of molecular profiling, minimally invasive diagnostics, and artificial intelligence-driven imaging interpretation to refine diagnostic accuracy and optimize treatment planning. Multidisciplinary tumor board discussions remain essential in tailoring individualized treatment strategies, balancing oncologic safety with quality of life. Ultimately, OBC exemplifies the challenges of managing rare malignancies and underscores the need for ongoing clinical trials and collaborative research efforts to establish evidence-based guidelines.

Keywords: Occult breast cancer; Neoadjuvant systemic threatment; Breast conserving surgery; SLNB

Referanslar

  1. GH F, Blijham G. Unexplained lymphadenopathy in family practice; An evaluation of the probability of malignant causes and the effectiveness of physicians' workup. Fam Pr. 1988;27:373-376.
  2. Copeland EM, Mcbride CM. Axillary Metastases from Unknown Primary Sites: Ann Surg. 1973;178(1):21-27. [Crossref]  [PubMed]  [PMC]
  3. Blanchard DK, Farley DR. Retrospective study of women presenting with axillary metastases from occult breast carcinoma. World J Surg. 2004;28:535-539. [Crossref]  [PubMed]
  4. Halsted WS. The results of radical operations for the cure of carcinoma of the breast. Ann Surg. 1907;46(1):1-19. [Crossref]  [PubMed]  [PMC]
  5. Owen HW. Occult carcinoma of the breast. Surg Gynecol Obstet. 1954;98:302-308. [PubMed]
  6. FITTS WT Jr, HORN RC Jr. Occult carcinoma of the breast. J Am Med Assoc. 1951;147(15):1429-1433. [Crossref]  [PubMed]
  7. Butler RS. 3.0 Tesla vs 1.5 Tesla breast magnetic resonance imaging in newly diagnosed breast cancer patients. World J Radiol. 2013;5(8):285. [Crossref]  [PubMed]  [PMC]
  8. Walker GV, Smith GL, Perkins GH, Oh JL, Woodward W, Yu T, et al. Population‐based analysis of occult primary breast cancer with axillary lymph node metastasis. Cancer. 2010;116(17):4000-4006. [Crossref]  [PubMed]  [PMC]
  9. Hessler LK, Molitoris JK, Rosenblatt PY, Bellavance EC, Nichols EM, Tkaczuk KHR, et al. Factors Influencing Management and Outcome in Patients with Occult Breast Cancer with Axillary Lymph Node Involvement: Analysis of the National Cancer Database. Ann Surg Oncol. 2017;24(10):29072914. [Crossref]  [PubMed]
  10. Patel J, Nemoto T, Rosner D, Dao TL, Pickren JW. Axillary lymph node metastasis from an occult breast cancer. Cancer. 1981;47(12):2923-2927. [Crossref]  [PubMed]
  11. Terada M, Miyashita M, Kumamaru H, Miyata H, Tamura K, Yoshida M, et al. Surgical treatment trends and identification of primary breast tumors after surgery in occult breast cancer: a study based on the Japanese National Clinical Database- Breast Cancer Registry. Breast Cancer. 2022;29(4):698-708. [Crossref]  [PubMed]
  12. Pangalis GA, Vassilakopoulos TP, Boussiotis VA, Fessas P. Clinical approach to lymphadenopathy. Semin Oncol. 1993;20(6):570-582. [PubMed]
  13. Weinstein SP, Localio AR, Conant EF, Rosen M, Thomas KM, Schnall MD. Multimodality Screening of HighRisk Women: A Prospective Cohort Study. J Clin Oncol. 2009;27(36):6124-6128. [Crossref]  [PubMed]  [PMC]
  14. Chan SW, Cheung PSY, Chan S, Lau SS, Wong TT, Ma M, et al. Benefit of Ultrasonography in the Detection of Clinically and Mammographically Occult Breast Cancer. World J Surg. 2008;32(12):2593-2598. [Crossref]  [PubMed]
  15. Yang L, Wang S, Zhang L, Sheng C, Song F, Wang P, et al. Performance of ultrasonography screening for breast cancer: a systematic review and meta-analysis. BMC Cancer. 2020;20(1):499. [Crossref]  [PubMed]  [PMC]
  16. Viggiano T, Scott R, Sharpe R, Kasper C, Mazza G, Pizzitola V, et al. Contrast Enhanced Mammography in Routine Clinical Practice: Frequency and Malignancy Rates of Enhancing Otherwise Occult Findings. Clin Breast Cancer. 2022;22(7):e736-e744. [Crossref]  [PubMed]
  17. Lee CW, Shin HJ, Kim HJ, Baek S, Park SY, Choi WJ, et al. Performance of high-resolution diffusion-weighted magnetic resonance imaging for detecting clinically occult ear ly breast cancers: a multi-reader study. Breast Cancer Res Treat. 2025;210(1):71-86. [Crossref]
  18. Kim HJ, Shin HJ, Baek S, Lee CW, Choi WJ, Chae EY, et al. High-resolution diffusion-weighted MRI plus mammography for detecting clinically occult breast cancers in women with dense breasts. Eur J Radiol. 2024;175:111440. [Crossref]  [PubMed]
  19. National Comprehensive Cancer Network (NCCN). (2025). NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Version 4.2025. Retrieved from org. [Link]
  20. Buchanan CL, Morris EA, Dorn PL, Borgen PI, Van Zee KJ. Utility of Breast Magnetic Resonance Imaging in Patients With Occult Primary Breast Cancer. Ann Surg Oncol. 2005;12(12):1045-1053. [Crossref]  [PubMed]
  21. Takabatake D, Taira N, Aogi K, Ohsumi S, Takashima S, Inoue T, et al. Two cases of occult breast cancer in which PETCT was helpful in identifying primary tumors. Breast Cancer. 2008;15(2):181-184. [Crossref]  [PubMed]
  22. Hu T, Zhang R, Zhang B, He S, Liu L, Zou Y, et al. Case report: Uncommon multiple metastases from occult breast cancer revealed by 68Ga-DOTATATE PET/CT. Front Oncol. 2023;13:1106890. [Crossref]  [PubMed]  [PMC]
  23. Ofri A, Moore K. Occult breast cancer: Where are we at? The Breast. 2020;54:211-215. [Crossref]  [PubMed]  [PMC]
  24. aron PL, Moore MP, Kinne DW, Candela FC, Osborne MP, Petrek JA. Occult breast cancer presenting with axillary metastases. Updated management. Arch Surg. 1990;125(2):210-214. [Crossref]  [PubMed]
  25. He M, Tang LC, Yu KD, Cao AY, Shen ZZ, Shao ZM, et al. Treatment outcomes and unfavorable prognostic factors in patients with occult breast cancer. Eur J Surg Oncol EJSO. 2012;38(11):1022-1028. [Crossref]  [PubMed]
  26. Wang X, Zhao Y, Cao X. Clinical Benefits of Mastectomy on Treatment of Occult Breast Carcinoma Presenting Axillary Metastases. Breast J. 2010;16(1):32-37. [Crossref]  [PubMed]
  27. Wang R, Yang H xin, Chen J, Huang J jun, Lv Q. Best treatment options for occult breast cancer: A meta-analysis. Front Oncol. 2023;13:1051232. [Crossref]  [PubMed]  [PMC]
  28. LaBella M, Lile-King RE, Agala CB, Spanheimer PM, Ollila DW, Gallagher KK, et al. Trends in management and related outcomes for occult primary breast cancer. Breast Cancer Res Treat. 2025;209(2):367-374. [Crossref]  [PubMed]
  29. Cohen BL, Collier AL, Kelly KN, Goel N, Kesmodel SB, Yakoub D, et al. Surgical Management of the Axilla in Patients with Occult Breast Cancer (cT0 N+) After Neoadjuvant Chemotherapy. Ann Surg Oncol. 2020;27(6):18301841. [Crossref]  [PubMed]
  30. Macedo FIB, Eid JJ, Flynn J, Jacobs MJ, Mittal VK. Optimal Surgical Management for Occult Breast Carcinoma: A Meta-analysis. Ann Surg Oncol. 2016;23(6):1838-1844. [Crossref]  [PubMed]
  31. Kim H, Park W, Kim SS, Ahn SJ, Kim YB, Kim TH, et al. Outcome of breast-conserving treatment for axillary lymph node metastasis from occult breast cancer with negative breast MRI. The Breast. 2020;49:63-69. [Crossref]  [PubMed]  [PMC]
  32. Tsai C, Zhao B, Chan T, Blair SL. Treatment for occult breast cancer: A propensity score analysis of the National Cancer Database. Am J Surg. 2020;220(1):153-160. [Crossref]  [PubMed]  [PMC]
  33. Zhao Z, Zhang T, Yao Y, Lu X. Clinicopathological characteristics and treatment outcomes of occult breast cancer: a population-based study. BMC Surg. 2022;22(1):143. [Crossref]  [PubMed]  [PMC]
  34. Li L, Zhang D, Wen T, Wu Y, Lv D, Zhai J, et al. Axillary lymph node dissection plus radiotherapy may be an optimal strategy for patients with occult breast cancer. J Natl Cancer Cent. 2022;2(4):198-204. [Crossref]  [PubMed]  [PMC]
  35. Kim H, Park W, Kim SS, Ahn SJ, Kim YB, Kim TH, Kim JH, et al. Prognosis of patients with axillary lymph node metastases from occult breast cancer: analysis of multicenter data. Radiat Oncol J. 2021;39(2):107-112. [Crossref]  [PubMed]  [PMC]
  36. Rueth NM, Black DM, Limmer AR, Gabriel E, Huo L, Fornage BD, et al. Breast Conservation in the Setting of Contemporary Multimodality Treatment Provides Excellent Outcomes for Patients with Occult Primary Breast Cancer. Ann Surg Oncol. 2015;22(1):90-95. [Crossref]  [PubMed]
  37. McCartan DP, Zabor EC, Morrow M, Van Zee KJ, El-Tamer MB. Oncologic Outcomes After Treatment for MRI Occult Breast Cancer (pT0N+). Ann Surg Oncol. 2017;24(11):31413147. [Crossref]  [PubMed]  [PMC]
  38. Vicini E, Galimberti V, Leonardi MC, Kahler-Ribeiro-Fontana S, Polizzi A, Petitto S, et al. Shifting from axillary dissection to targeted axillary surgery after neoadjuvant treatment: the evolving management of occult breast cancer in a monoinstitutional series of 114 patients. Breast Cancer Res Treat. 2025;210(3):661-672. [Crossref]  [PubMed]
  39. Botty Van Den Bruele A, Lavery J, Plitas G, Pilewskie ML. Axillary Downstaging in Occult Primary Breast Cancer After Neoadjuvant Chemotherapy. Ann Surg Oncol. 2021;28(2):968-974. [Crossref]  [PubMed]  [PMC]
  40. Man X, Xu H, Wang H, Zhao J, Chen X, Yin S, et al. Survival analysis and nomogram for early-stage occult breast cancer with positive lymph nodes based on the SEER database. Ann Transl Med. 2022;10(24):1351-1351. [Crossref]  [PubMed]  [PMC]