Abstract P4-08-03: Looking forward to the TNM 9th edition: Is it time to stage the different breast cancer subtypes as distinct diseases?
Authors: Nichol AM , Lohrisch CA , Gondara L , Speers C , Gelmon KA 
Published: May 2019

Background: For clinical purposes, four subtypes of breast cancer: Luminal A (LumA), Luminal B (LumB), Her2-positive (H2P) and Triple-Negative (TN) are commonly recognized. This study investigated staging them independently as different diseases. The hypothesis was that the anatomic staging system of the 8th TNM edition would have good prognostic performance within each breast cancer subtype, as defined by estrogen receptor (ER), progesterone receptor (PR), Her2 amplification (H2) and grade.

Methods: Using the Breast Cancer Outcomes Unit database, we identified patients treated without neoadjuvant therapy between 2005 and 2009, when use of anti-Her2 therapy (AH2T) was routine for H2+ disease. We approximated the four subtypes of breast cancer described in Table 48.2 of the revised January 25, 2018 version of the TNM 8th edition (https://cancerstaging.org/references-tools/deskreferences/Pages/Breast-Cancer-Staging.aspx) as follows: LumA ER3+ AND PR3+ AND H2- AND (G1-2); LumB All Non-LumA (ER+ OR PR+) AND H2-; H2P All H2+; and TN ER- AND PR- AND H2-. Breast cancer-specific survival (BCSS) was determined for anatomic stages I-IV within each subtype by the Kaplan-Meier method. The predominant usage of hormone therapy (HT), chemotherapy (ChT) and AH2T was compared by subtype for patients &lt; 70 years, who were generally eligible for ChT.

Results: The median follow-up for the 8,640 patients was 10.0 years. The numbers of patients within each subtype were: LumA = 2,288, LumB = 4,097, H2P = 1,374, and TN = 881. The predominant systemic therapies used by subtype were: LumA: HT = 60.2% and HT+ChT = 29.8%; LumB: HT = 45.9% and HT+ChT = 42.1%; H2P: HT+ChT+AH2 = 40.1% and ChT+AH2 = 35.0%; and TN: ChT = 79.1%. The confidence intervals for BCSS in stages I, II, III, and IV were distinct for the four subtypes, as shown in Table 1.

BCSS by Stage for Clinical Breast Cancer Subtypes1-year BCSSLumA (%) (CI)LumB (%) (CI)H2P (%) (CI)TN (%) (CI)Stage I98.1 (97.0, 98.8)96.5 (95.5, 97.2)95.4 (92.9, 97.0)90.4 (86.5, 93.2)Stage II93.4 (91.1, 95.1)86.5 (84.6, 88.3)87.2 (84.1, 89.7)81.4 (77.3, 84.9)Stage III79.9 (71.8, 85.9)66.1 (61.5, 70.3)74.0 (68.1, 78.9)58.0 (48.3, 66.5)Stage IV42.9 (17.7, 66.0)16.9 (8.1, 28.6)33.1 (18.6, 48.3)0.0 (0.0, 0.0)

Conclusions: The anatomic staging system provided reliable BCSS prognostication within breast cancer subtypes. Individualizing treatment using anatomic staging within breast cancer subtypes, would permit decisions about the volume of radiotherapy and the need for intensification of systemic therapy to be made using the familiar and time-tested risk metric of disease extent. In the future, as breast cancer subtyping becomes more sophisticated, prognostication using anatomic staging within these distinct diseases should become increasingly accurate.

Citation Format: Nichol AM, Lohrisch CA, Gondara L, Speers C, Gelmon KA. Looking forward to the TNM 9th edition: Is it time to stage the different breast cancer subtypes as distinct diseases? [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-03.