Risk Factors of Response to Neoadjuvant Chemotherapy in Patients with Luminal (HER2 Negative) Breast Cancer: Roc Curve and Logistic Regression Model Results RF of response to NAC in HER2- BC

Atilla Bozdogan (1), Selman Emiroglu (2), Asmaa Abuaisha (3), Ozlem Deniz Basar (4)
(1) Department of Statistics, Institute of Science, Istanbul Ticaret University, Istanbul, Turkey, Turkey,
(2) Breast Surgery Division, Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey, Turkey,
(3) Genetics Department, Institute of Graduate Studies in Health Sciences, Istanbul University, Istanbul, Turkey, Turkey,
(4) Department of Statistics, Institute of Science, Istanbul Ticaret University, Istanbul, Turkey, Turkey


Background: Neoadjuvant chemotherapy (NAC) is less effective for luminal human epidermal growth factor receptor 2 (HER2) negative breast cancer (BC) patients and generally shows a low pathological complete response (pCR) after NAC compared to HER2 positive and triple negative breast cancer (TNBC). This study aimed to determine the factors associated with histopathologic response following NAC in luminal (HER2 negative) BC.

Methods: This is a cross-sectional study conducted on 255 estrogen (ER) positive and HER2 negative BC patients after NAC between January 2018 and July 2023. Demographic and clinicopathological characteristics of the patients were collected for the statistical analysis. Chi-Square tests were used in the qualitative comparisons between study groups. Receiver Operating Characteristic (ROC) analysis was used for the diagnostic performance of Ki-67 expression and ER in determining the pCR rates. Using the Youden index, optimum cut points were determined. Also, multivariate logistic regression analysis was applied to determine the independent variables associated with the dependent variable (pCR).

Results: After NAC, pCR was achieved in the breast in 35 (14%) patients, in the axilla in 44 (17%) patients, and in both the breast and axilla in 18 (7%) patients. Ki-67 expression was the only common variable associated with the breast, axilla and both the breast and axilla pCR. The most appropriate Ki-67 expression cut-off value for determining the breast and axilla complete response was found to be 40%. ER positivity level was only associated with pCR in the breast and the cut-off value was found to be 85%.

Conclusion: The results of this study raise the possibility of patients with luminal (HER2 negative) BC with Ki-67 expression higher than 40% benefiting from chemotherapy, as they showed increased pCR rates.

Full text article

Generated from XML file


Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747-52. doi: 10.1038/35021093.

Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A. 2003;100(14):8418-23. doi: 10.1073/pnas.0932692100.

Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B, Senn HJ. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol. 2013;24(9):2206-23. doi: 10.1093/annonc/mdt303.

Höller A, Nguyen-Sträuli BD, Frauchiger-Heuer H, Ring A. "Diagnostic and Prognostic Biomarkers of Luminal Breast Cancer: Where are We Now?". Breast Cancer (Dove Med Press). 2023;15:525-40. doi: 10.2147/BCTT.S340741.

Horimoto Y, Arakawa A, Tanabe M, Sonoue H, Igari F, Senuma K, et al. Ki67 expression and the effect of neo-adjuvant chemotherapy on luminal HER2-negative breast cancer. BMC Cancer. 2014;14:550. doi: 10.1186/1471-2407-14-550.

King TA, Morrow M. Surgical issues in patients with breast cancer receiving neoadjuvant chemotherapy. Nat Rev Clin Oncol. 2015;12(6):335-43. doi: 10.1038/nrclinonc.2015.63.

Kim HS, Yoo TK, Park WC, Chae BJ. Potential Benefits of Neoadjuvant Chemotherapy in Clinically Node-Positive Luminal Subtype(-) Breast Cancer. J Breast Cancer. 2019;22(3):412-24. doi: 10.4048/jbc.2019.22.e35.

Boughey JC, Alvarado MD, Lancaster RB, Fraser Symmans W, Mukhtar R, Wong JM, et al. Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint. NPJ Breast Cancer. 2018;4:26. doi: 10.1038/s41523-018-0074-6.

Wong SM, Weiss A, Mittendorf EA, King TA, Golshan M. Surgical Management of the Axilla in Clinically Node-Positive Patients Receiving Neoadjuvant Chemotherapy: A National Cancer Database Analysis. Ann Surg Oncol. 2019;26(11):3517-25. doi: 10.1245/s10434-019-07583-6.

Vila J, Mittendorf EA, Farante G, Bassett RL, Veronesi P, Galimberti V, et al. Nomograms for Predicting Axillary Response to Neoadjuvant Chemotherapy in Clinically Node-Positive Patients with Breast Cancer. Ann Surg Oncol. 2016;23(11):3501-9. doi: 10.1245/s10434-016-5277-1.

von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30(15):1796-804. doi: 10.1200/JCO.2011.38.8595.

Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164-72. doi: 10.1016/S0140-6736(13)62422-8.

Haque W, Verma V, Hatch S, Suzanne Klimberg V, Brian Butler E, Teh BS. Response rates and pathologic complete response by breast cancer molecular subtype following neoadjuvant chemotherapy. Breast Cancer Res Treat. 2018;170(3):559-67. doi: 10.1007/s10549-018-4801-3.

Kim SY, Cho N, Choi Y, Lee SH, Ha SM, Kim ES, et al. Factors Affecting Pathologic Complete Response Following Neoadjuvant Chemotherapy in Breast Cancer: Development and Validation of a Predictive Nomogram. Radiology. 2021;299(2):290-300. doi: 10.1148/radiol.2021203871.

Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11(16):5678-85. doi: 10.1158/1078-0432.CCR-04-2421.

Boughey JC, McCall LM, 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;260(4):608-14; discussion 14-6. doi: 10.1097/SLA.0000000000000924.

Yerushalmi R, Woods R, Ravdin PM, Hayes MM, Gelmon KA. Ki67 in breast cancer: prognostic and predictive potential. Lancet Oncol. 2010;11(2):174-83. doi: 10.1016/S1470-2045(09)70262-1.

Yoshioka T, Hosoda M, Yamamoto M, Taguchi K, Hatanaka KC, Takakuwa E, et al. Prognostic significance of pathologic complete response and Ki67 expression after neoadjuvant chemotherapy in breast cancer. Breast Cancer. 2015;22(2):185-91. doi: 10.1007/s12282-013-0474-2.

Burcombe R, Wilson GD, Dowsett M, Khan I, Richman PI, Daley F, et al. Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer. Breast Cancer Res. 2006;8(3):R31. doi: 10.1186/bcr1508.

Jones RL, Salter J, A'Hern R, Nerurkar A, Parton M, Reis-Filho JS, et al. The prognostic significance of Ki67 before and after neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat. 2009;116(1):53-68. doi: 10.1007/s10549-008-0081-7.

Fasching PA, Heusinger K, Haeberle L, Niklos M, Hein A, Bayer CM, et al. Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. BMC Cancer. 2011;11:486. doi: 10.1186/1471-2407-11-486.

Matsubara N, Mukai H, Fujii S, Wada N. Different prognostic significance of Ki-67 change between pre- and post-neoadjuvant chemotherapy in various subtypes of breast cancer. Breast Cancer Res Treat. 2013;137(1):203-12. doi: 10.1007/s10549-012-2344-6.

Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471-4. doi: 10.1245/s10434-010-0985-4.

Kaufmann M, von Minckwitz G, Bear HD, Buzdar A, McGale P, Bonnefoi H, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006. Ann Oncol. 2007;18(12):1927-34. doi: 10.1093/annonc/mdm201.

Kim SI, Sohn J, Koo JS, Park SH, Park HS, Park BW. Molecular subtypes and tumor response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. Oncology. 2010;79(5-6):324-30. doi: 10.1159/000322192.

Prat A, Fan C, Fernández A, Hoadley KA, Martinello R, Vidal M, et al. Response and survival of breast cancer intrinsic subtypes following multi-agent neoadjuvant chemotherapy. BMC Med. 2015;13:303. doi: 10.1186/s12916-015-0540-z.

Collins PM, Brennan MJ, Elliott JA, Abd Elwahab S, Barry K, Sweeney K, et al. Neoadjuvant chemotherapy for luminal a breast cancer: Factors predictive of histopathologic response and oncologic outcome. Am J Surg. 2021;222(2):368-76. doi: 10.1016/j.amjsurg.2020.11.053.

Li F, Ma L, Geng C, Liu C, Deng H, Yue M, et al. Analysis of the relevance between molecular subtypes and efficacy of neoadjuvant chemotherapy in breast cancer as well as its prognostic factors. Pathol Res Pract. 2018;214(8):1166-72. doi: 10.1016/j.prp.2018.06.010.

Lee H, Lee DE, Park S, Kim TS, Jung SY, Lee S, et al. Predicting Response to Neoadjuvant Chemotherapy in Patients With Breast Cancer: Combined Statistical Modeling Using Clinicopathological Factors and FDG PET/CT Texture Parameters. Clin Nucl Med. 2019;44(1):21-9. doi: 10.1097/RLU.0000000000002348.

Li Y, Zhang J, Wang B, Zhang H, He J, Wang K. A nomogram based on clinicopathological features and serological indicators predicting breast pathologic complete response of neoadjuvant chemotherapy in breast cancer. Sci Rep. 2021;11(1):11348. doi: 10.1038/s41598-021-91049-x.

Tan MC, Al Mushawah F, Gao F, Aft RL, Gillanders WE, Eberlein TJ, Margenthaler JA. Predictors of complete pathological response after neoadjuvant systemic therapy for breast cancer. Am J Surg. 2009;198(4):520-5. doi: 10.1016/j.amjsurg.2009.06.004.


Atilla Bozdogan
atillabozdogan@gmail.com (Primary Contact)
Selman Emiroglu
Asmaa Abuaisha
Ozlem Deniz Basar
Bozdogan A, Emiroglu S, Abuaisha A, Basar OD. Risk Factors of Response to Neoadjuvant Chemotherapy in Patients with Luminal (HER2 Negative) Breast Cancer: Roc Curve and Logistic Regression Model Results: RF of response to NAC in HER2- BC. Arch Breast Cancer [Internet]. 2024 Jan. 31 [cited 2024 Feb. 22];11(1):67-74. Available from: https://archbreastcancer.com/index.php/abc/article/view/841

Article Details

Similar Articles

You may also start an advanced similarity search for this article.