Triple-Negative Phenotype Boosts Prognostic Power of Traditional Staging

Incorporating receptor status could improve TNM staging prognostic accuracy for women with ductal breast carcinoma

medwireNews: The tumour node metastasis (TNM) staging system for breast cancer should take into consideration the triple-negative Phenotype (TNP), US researchers believe.

The team found that adjusting for oestrogen receptor (ER), progesterone receptor (PR), and human Epidermal growth factor 2 (HER2) status during TNM staging significantly altered the prognosis of 1842 women with primary invasive ductal breast carcinoma.

Over a median of 4.3 years of follow-up, the survival of the 15.2% of women with TNP breast cancer was comparable to that of the women with non-TNP disease that was one stage higher, report Armando Giuliano, from Cedars-Sinai Medical Center in Los Angeles, California, and co-workers.

Thus, the 5-year overall survival for women with stage I TNP was similar to that of women with non-TNP stage II disease (92.2% vs. 93.4%), while stage II TNP matched stage III non-TNP (83.9% vs. 78.5%) and stage III TNP approached that of stage IV non-TNP (58.4% vs. 34.6%). For women with stage IV TNP tumours, the 5-year overall survival rate fell to 14.3%.

Adjusting the TNM staging system to upstage all patients with TNP breast cancer altered the TNM stage of around 15% of patients. Of note, the number of patients with stage I disease significantly decreased from 51.1% with TNM alone to 44.6% when including TNP, the researchers report in JAMA Surgery.

Moreover, multivariate analysis showed that age (hazard ratio [HR]=1.05), tumour (HR=1.59), node (HR=1.44), metastasis (HR=5.45), and TNP phenotype (HR=2.71) all significantly predicted 5-year overall survival. And the addition of TNP phenotype – also known as TNM-Biology (B) – to the staging system significantly improved its prognostic value.

“Stage reclassification that incorporates TNP status can be a first step in recognizing the importance of nonanatomic factors in the staging of breast cancer and could help clinicians provide better cancer care,” says the team.

“This study provides a preliminary proof of principle that the breast cancer staging system could be improved by the inclusion of biomarkers that complement TNM and are available worldwide.”


Bagaria SP, Ray PS, Sim M, et al. Personalizing Breast Cancer Staging by the Inclusion of ER, PR, and HER2. JAMA Surg Advance online publication December 4, 2013. doi:10.1001/jamasurg.2013.3181.

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