Accuracy of Cytological Evaluation for Breast Cancer Detection in Patients with Pathologic Nipple Discharge: A Meta-Analysis

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Accuracy of Cytological Evaluation for Breast Cancer Detection in Patients with Pathologic Nipple Discharge: A Meta – Analysis

Nipple discharge is a common issue in breast disease patients. It can be a sign of various conditions, including underlying malignancies. This meta – analysis aimed to evaluate the diagnostic value of nipple discharge cytology in detecting breast cancer.

Introduction

Nipple discharge is not only a common complaint but also a potential indicator of breast problems. Diagnostic imaging methods like mammography and ultrasound have limitations. For example, a retrospective analysis showed that mammography and sonography alone or combined were less sensitive for non – palpable breast cancer with nipple discharge. MRI also has its drawbacks in some cases. Galactography and fiberoptic ductoscopy are invasive, and their accuracy varies. Nipple discharge cytology, being simple, non – invasive, and inexpensive, could be a useful addition.

Methods

  • Search Strategy: Searched international databases (Medline/PubMed, Embase, Cochrane Library, Google Scholar) from January 2000 to October 2018 using relevant keywords. Also checked existing reviews, bibliographies, etc.
  • Inclusion and Exclusion Criteria: Studies had to have histopathological confirmation of breast cancer, provide data for 2×2 contingency tables (sensitivity and specificity), assess cytology in pathological nipple discharge patients, have a control group, and be restricted to breast cancer and control patients. Excluded case reports, review articles, etc.
  • Data Extraction and Quality Assessment: Two reviewers extracted data (author, year, country, age, method of discharge collection, number of patients, sensitivity, and specificity). Quality was assessed using QUADAS – 2.
  • Statistical Analysis: Used STATA SE 12.0 and Meta – DiSc 1.4. Calculated sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and summary receiver operating characteristic curve. Assessed heterogeneity (Cochran Q test, I² statistic), publication bias (Deeks’ funnel regression), and performed sensitivity analysis.

Results

  • Included Studies: Initially found 286 articles. After screening, 12 studies with 1476 patients were included.
  • Study Characteristics and Quality Assessment: 219 reference – positive and 1257 reference – negative subjects. Studies from 4 countries (China, USA, Japan, Bulgaria). Sample sizes from 27 to 434. Six studies used nipple squeezing, six used ductal lavages (including TCT). Most studies had low risk of bias.
  • Data Analysis:
    • Pooled sensitivity was 63% (95% CI: 53%–72%), specificity 95% (95% CI: 87%–98%).
    • Positive likelihood ratio 12.35 (95% CI: 4.87–31.34), negative likelihood ratio 0.39 (95% CI: 0.30–0.50).
    • Diagnostic odds ratio 31.88 (95% CI: 11.30–89.98). Area under the curve was 0.79 (95% CI: 0.75–0.82).
  • Publication Bias: P value of 0.169 indicated no publication bias.
  • Sensitivity Analysis: Results were stable.
  • Threshold Effect and Heterogeneity: No significant heterogeneity from threshold effect (Spearman correlational coefficient 0.014, P = 0.966). Meta – regression showed no contribution from region, method of discharge collection, or sample size. Sub – group analysis showed method of discharge collection (squeezing vs. ductal lavage) was a source of heterogeneity.

Discussion

  • Diagnostic Value: The meta – analysis suggests nipple discharge cytology has moderate sensitivity and high specificity. The diagnostic odds ratio (31.88) and area under the curve (0.79) support its usefulness.
  • Sub – group Analysis: Squeezing the nipple had more heterogeneity. Ductal lavage may be more reliable as it increases cell exfoliation (e.g., often combined with FDS or galactography, and TCT improves detection rate).
  • Limitations: Most studies from Asian countries (may limit generalizability). Heterogeneity in specificity. Pooling of data with different positive cell baselines.

Conclusion

Nipple discharge cytology is a useful diagnostic modality for breast cancer in patients with pathological nipple discharge. However, more large – scale, prospective, multicenter studies are needed to confirm these findings.

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doi:10.1097/CM9.0000000000000643

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