Predictive Value of IHC4 Score for Pathological Response to Neoadjuvant Chemotherapy in Hormone Receptor-Positive Breast Cancer

  • Published : 2015.12.03


Purpose: This study aimed to explore the value of IHC4 in predicting pathological response after neoadjuvant chemotherapy in patients with hormonal receptor (HR)-positive breast cancer (BC). Materials and Methods: In this retrospective exploratory study, data for 68 HR-positive BC patients who received neoadjuvant chemotherapy were recorded. IHC4 scores were calculated based on estrogen receptors/progesterone receptors, Ki-67 and HER2 status. Logistic and ordinal regression analyses in addition to likelihood ratio test were used to explore associations of IHC4 scores and other clinico-pathological parameters with pathological complete response (pCR) and pathological stage. Results: Taking the 25th percentile as the cut-off, a lower IHC4 score was associated with an increased probability of pCR (low; 52.9% vs. High; 21.6%, OR=4.1, 95% CI=1.28-13.16, p=0.018) and a lower pathological stage (OR=3.9, 95% CI=1.34-11.33, p=0.012). When the IHC4 score was treated as a continuous variable, a lower score was again associated with an increased probability of pCR (OR=1.010, 95% CI=1.001-1.018, p=0.025) and lower pathological stage (OR=1.009, 95% CI=1.002-1.017, P=0.008). Lower clinical stage was associated with a better pCR rate that was of borderline significance (P=0.056). When clinical stage and IHC4 score were incorporated together in a logistic model, the likelihood ratio test gave a P-value of 0.004 after removal of the IHC4 score and 0.011 after removal of the stage, indicating a more significant predictive value of the IHC4 score for pCR. Conclusions: This study suggests that the IHC4 score can predict pathological response to neoadjuvant chemotherapy in HR-positive BC patients. This finding now needs to be validated in a larger cohort of patients.


  1. Aapro M (2011). Neoadjuvant therapy in breast cancer: can we define its role? The Oncologist, 6, 36-39.
  2. Barrios CH, Sampaio C, Vinholes J, et al (2009). What is the role of chemotherapy in estrogen receptor-positive, advanced breast cancer? Ann Oncol, 20, 1157-62.
  3. Bear HD, Anderson S, Brown A, et al (2003). The effect on tumour response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol, 21, 4165-74.
  4. Chang JC, Makris A, Gutierrez MC, et al (2008). Gene expression patterns in formalin-fixed, paraffin-embedded core biopsies predict docetaxel chemosensitivity in breast cancer patients. Breast Cancer Res Treat, 108, 233-40.
  5. Christiansen J, Bartlett J, Gustavson M, et al (2012). Validation of IHC4 algorithms for prediction of risk of recurrence in early breast cancer using both conventional and quantitative IHC approaches. J Clin Oncol, 30, 517.
  6. Colleoni M, Montagna E (2012). Neoadjuvant therapy for ERpositive breast cancers. Ann Oncol, 23, 243-48.
  7. Colleoni M, Viale G, Zahrieh D, et al (2004). Chemotherapy is more effective in patients with breast cancer not expressing steroid hormone receptors: a study of preoperative treatment. Clin Cancer Res, 10, 6622-8.
  8. Cortazar P, Zhang L, Untch M, et al (2014). Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet, 384, 164-72.
  9. Cuzick J, Dowsett M, Pineda S, et al (2011). Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor-2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer. J Clin Oncol, 29, 4273-8.
  10. Dowsett M, Cuzick J, Wale C, et al (2010). Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study. J Clin Oncol, 28, 1829-34.
  11. Gianni L, Eiermann W, Semiglazov V, et al (2010). Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet, 375, 377-84.
  12. Gianni L, Zambetti M, Clark K, et al (2005). Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol, 23, 7265-77.
  13. Kim MM, Allen P, Gonzalez-Angulo AM, et al (2013). Pathologic complete response to neoadjuvant chemotherapy with trastuzumab predicts for improved survival in women with HER2-overexpressing breast cancer. Ann Oncol, 24, 1999-2004.
  14. Kaufmann M, Von Minckwitz G, Mamounas EP, et al (2012). Recommendations from an International consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol, 19, 1508-16.
  15. Lonning PE (2012). Poor-prognosis estrogen receptor- positive disease: present and future clinical solutions. Ther Adv Med Oncol, 4, 127-37.
  16. Penault-Llorca F, Andre F, Sagan C, et al (2009). Ki67 Expression and docetaxel efficacy in patients with estrogen receptor-positive breast cancer. J Clin Oncol, 27, 2809-15.
  17. Peto R, Davies C, Godwin J, et al (2012). Comparisons between different polychemotherapy regimens for early breast cancer meta-analysis of long-term outcome among 100.000 women in 123 randomised trials. Lancet, 379, 432-44.
  18. Telli ML (2013). Insight or confusion: survival after responseguided neoadjuvant chemotherapy in breast cancer. J Clin Oncol, 31, 3613-5.
  19. Untch M, Fasching PA, Konecny GE, et al (2011). Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favourable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO Trial of the AGO and GBG Study Groups. J Clin Oncol, 29, 3351-7.
  20. Von Minckwitz G, Untch M, Nuesch E, et al (2011). Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neoadjuvant chemotherapy trials. Breast Cancer Res Treat, 125, 145-56.

Cited by

  1. Pathologic diagnosis of breast cancer patients: evolution of the traditional clinical-pathologic paradigm toward “precision” cancer therapy vol.92, pp.3, 2017,