Incorporation of Treatment Response, Tumor Grade and Receptor Status Improves Staging Quality in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy
- 327 Downloads
Improved staging systems that better predict survival for breast cancer patients who receive neoadjuvant chemotherapy (NAC) by accounting for clinical pathological stage plus estrogen receptor (ER) and grade (CPS+EG) and ERBB2 status (Neo-Bioscore) have been proposed. We sought to evaluate the generalizability and performance of these staging systems in a national cohort.
The National Cancer Database (2006–2012) was reviewed for patients with breast cancer who received NAC and survived ≥90 days after surgery. Four systems were evaluated: clinical/pathologic American Joint Committee on Cancer (AJCC) 7th edition, CPS+EG, and Neo-Bioscore. Unadjusted Kaplan–Meier analysis and adjusted Cox proportional hazards models quantified overall survival (OS). Systems were compared using area under the curve (AUC) and integrated discrimination improvement (IDI).
Overall, 43,320 patients (5-year OS 76.0, 95% confidence interval [CI] 75.4–76.5%) were included, 12,002 of whom had evaluable Neo-Bioscore. AUC at 5 years for CPS+EG (0.720, 95% CI 0.714–0.726) and Neo-Bioscore (0.729, 95% CI 0.716–0.742) were improved relative to AJCC clinical (0.650, 95% CI 0.643–0.656) and pathologic (0.683, 95% CI 0.676–0.689) staging. Both CPS+EG (IDI 7.2, 95% CI 6.6–7.7%) and Neo-Bioscore (IDI 9.8, 95% CI 8.0–11.6%) demonstrated superior discrimination when compared with AJCC clinical staging at 5 years. Comparison of CPS+EG with Neo-Bioscore yielded an IDI of 2.6% (95% CI 0.9–4.5%), indicating that Neo-Bioscore is the best staging system.
In a heterogenous national cohort of breast cancer patients treated with NAC and surgery, the incorporation of chemotherapy response, tumor grade, ER status, and ERBB2 status into the staging system substantially improved on the AJCC TNM staging system in discrimination of OS. Neo-Bioscore provided the best staging discrimination.
The NCDB is a joint project of the CoC of the American College of Surgeons and the American Cancer Society. The data used are derived from a de-identified NCDB PUF. The American College of Surgeons and the CoC have not verified, and are not responsible for, the analytic or statistical methods or the conclusions drawn from these data by the investigators. The authors gratefully acknowledge the support of the Mayo Clinic Department of Surgery and the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery as substantial contributors of resources to the project. Additionally, Dr. Bergquist acknowledges the support of the Mayo Clinic Clinician Investigator Training Program for salary support. Finally, we would like to thank the Society of Surgical Oncology for affording us the opportunity to present this work at their annual Cancer Symposium in March 2017. Additionally, Dr. Bergquist acknowledges the Susan G Komen for the Cure foundation for their support of his attendance at the SSO meeting with their annual Breast Cancer research award.
Conflicts of interest
John R. Bergquist, Brittany L. Murphy, Curtis B. Storlie, Elizabeth B. Habermann, and Judy C. Boughey disclose no conflicts of interest.
The Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery provides salary support for Dr. Habermann and Dr. Murphy. Dr. Bergquist receives salary support from the Mayo Clinic Clinician Investigator Training program. The conduct and presentation of this research was independent of the above funding sources. This work has not previously, or concurrently, been submitted for publication.
- 2.Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997;15(7):2483–93.CrossRefPubMedGoogle Scholar
- 5.Boughey JC, McCall LMM, Ballman KV, Mittendorf EA, Ahrendt GM, Wilke LG, et al. Tumor biology correlates with rates of breast-conserving surgery and pathologic complete response after neoadjuvant chemotherapy for breast cancer: findings from the ACOSOG Z1071 (Alliance) Prospective Multicenter Clinical Trial. Ann Surg. 2014. 2014;260(4):608–16.Google Scholar
- 10.Schwartz AM, Henson DE, Chen D, Rajamarthandan S. Histologic grade remains a prognostic factor for breast cancer regardless of the number of positive lymph nodes and tumor size: A study of 161 708 cases of breast cancer from the SEER program. Arch Pathol Lab Med. 2014;138(8):1048–52.CrossRefPubMedGoogle Scholar
- 11.Edge SB, American Joint Committee on Cancer. AJCC cancer staging manual, 8th ed. American Joint Committee on Cancer; 2017. p. 1024.Google Scholar
- 14.Yi M, Mittendorf EA, Cormier JN, Buchholz TA, Bilimoria K, Sahin AA, et al. Novel staging system for predicting disease-specific survival in patients with breast cancer treated with surgery as the first intervention: time to modify the current American Joint Committee on Cancer staging system. J Clin Oncol. 2011;29(35):4654–61.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.R Core Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2016. https://www.r-project.org.
- 31.Swisher SK, Vila J, Tucker SL, Bedrosian I, Shaitelman SF, Litton JK, et al. Locoregional control according to breast cancer subtype and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast-conserving therapy. Ann Surg Oncol. 2016;23(3):749–56.CrossRefPubMedGoogle Scholar
- 37.Swain SM, Kim SB, Cortés J, Ro J, Semiglazov V, Campone M, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013;14(6):461–71.CrossRefPubMedPubMedCentralGoogle Scholar