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The role of immunohistochemistry in breast cancer patients treated with neoadjuvant chemotherapy: an old tool with an enduring prognostic value.
Clin Breast Cancer. 2013 Apr; 13(2):146-52.CB

Abstract

BACKGROUND

To assess the molecular subtypes determined by hormonal receptors (HR) and human epidermal growth factor receptor 2 (HER2) status and the role of proliferation measured by the Ki-67 marker as predictive and prognostic factors in breast cancer patients treated with neoadjuvant chemotherapy.

METHODS

A total of 127 breast cancer patients were treated with neoadjuvant chemotherapy every 2 weeks as part of 2 studies. Study A consisted of the administration of Adriamycin (40 mg/m(2)) on day 1 plus paclitaxel (150 mg/m(2)) and gemcitabine 2000 mg/m(2)) on day 2 for 6 cycles (n = 54). Study B consisted of the administration of epirubicin (90 mg/m(2)), cyclophosphamide (600 mg/m(2)) on day 1 for 3 cycles, followed by the administration of paclitaxel (150 mg/m(2)) and gemcitabine 2500 (mg/m(2)) on day 1 with or without trastuzumab according to HER2 status (n = 73). In study A, patients did not receive trastuzumab regardless of HER2 status. The molecular subtypes of the patients with breast cancer were classified as 49% HR(+)/HER2(-), 17.5% HR(+)/HER2(+), 13.5% HR(-)/HER2(+), and 20% HR(-)/HER2(-).

RESULTS

Pathologic complete response (pCR), defined as the absence of invasive cells in the breast and the lymph nodes, was achieved in 35 (28%) patients. The pCR rate was significantly different between the molecular subtypes of breast cancer, with 9% in HR(+)/HER2(-), 23% in HR(+)/HER2(+), 50% in HR(-)/HER2(+), and 56% in HR(-)/HER2(-) tumors (P < .001). The pCR rate was significantly higher in tumors that had high Ki-67 (≥20%) expression and were HR(-). HER2(+) was associated with a higher trend of pCR but did not reach statistical significance. The median follow-up was 81 months (r = 15-150 months). Patients who achieved a pCR had a significantly lower recurrence (P = .01) and higher overall survival (P = .02) compared with those who did not achieve pCR. A multivariate analysis revealed that pCR (hazard ratio 0.24 [95% CI, 0.07-0.7]; P = .019), the molecular subtype (hazard ratio 0.3 [95% CI, 0.1-0.8]; P = .02), and the Ki-67 index (hazard ratio 3.2 [95% CI, 1.4-7.1]; P = .004) were significant independent predictors of disease-free survival. Similar results were obtained for overall survival, in which the pCR rate (hazard ratio 0.119 [95% CI, 0.028-0.5]; P = .004), the molecular subtype (hazard ratio 0.17 [95% CI, 0.03-0.86]; P = .02), and the Ki-67 index (hazard ratio 3.6 [95% CI, 1.3-9.7]; P = .01) also displayed a significant influence on survival.

CONCLUSIONS

Molecular subtypes and Ki-67 index were independent prognostic factors for disease-free survival and overall survival in breast cancer patients treated with neoadjuvant chemotherapy. A high rate of Ki-67 and HR(-) expression were predictors of pCR.

Authors+Show Affiliations

Medical Oncology Service, Hospital Universitario Virgen de la Victoria de Málaga, Málaga, Spain. asmoncomed@yahoo.esNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Journal Article

Language

eng

PubMed ID

23318089

Citation

Sánchez-Muñoz, Alfonso, et al. "The Role of Immunohistochemistry in Breast Cancer Patients Treated With Neoadjuvant Chemotherapy: an Old Tool With an Enduring Prognostic Value." Clinical Breast Cancer, vol. 13, no. 2, 2013, pp. 146-52.
Sánchez-Muñoz A, Plata-Fernández YM, Fernández M, et al. The role of immunohistochemistry in breast cancer patients treated with neoadjuvant chemotherapy: an old tool with an enduring prognostic value. Clin Breast Cancer. 2013;13(2):146-52.
Sánchez-Muñoz, A., Plata-Fernández, Y. M., Fernández, M., Jaén-Morago, A., Fernández-Navarro, M., de la Torre-Cabrera, C., Ramirez-Tortosa, C., Lomas-Garrido, M., Llácer, C., Navarro-Perez, V., Alba-Conejo, E., & Sánchez-Rovira, P. (2013). The role of immunohistochemistry in breast cancer patients treated with neoadjuvant chemotherapy: an old tool with an enduring prognostic value. Clinical Breast Cancer, 13(2), 146-52. https://doi.org/10.1016/j.clbc.2012.11.006
Sánchez-Muñoz A, et al. The Role of Immunohistochemistry in Breast Cancer Patients Treated With Neoadjuvant Chemotherapy: an Old Tool With an Enduring Prognostic Value. Clin Breast Cancer. 2013;13(2):146-52. PubMed PMID: 23318089.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of immunohistochemistry in breast cancer patients treated with neoadjuvant chemotherapy: an old tool with an enduring prognostic value. AU - Sánchez-Muñoz,Alfonso, AU - Plata-Fernández,Yessica Maria, AU - Fernández,Margarita, AU - Jaén-Morago,Ana, AU - Fernández-Navarro,Monica, AU - de la Torre-Cabrera,Capilla, AU - Ramirez-Tortosa,Cesar, AU - Lomas-Garrido,Maria, AU - Llácer,Casilda, AU - Navarro-Perez,Victor, AU - Alba-Conejo,Emilio, AU - Sánchez-Rovira,Pedro, Y1 - 2013/01/11/ PY - 2012/08/08/received PY - 2012/10/07/revised PY - 2012/11/08/accepted PY - 2013/1/16/entrez PY - 2013/1/16/pubmed PY - 2013/9/13/medline SP - 146 EP - 52 JF - Clinical breast cancer JO - Clin Breast Cancer VL - 13 IS - 2 N2 - BACKGROUND: To assess the molecular subtypes determined by hormonal receptors (HR) and human epidermal growth factor receptor 2 (HER2) status and the role of proliferation measured by the Ki-67 marker as predictive and prognostic factors in breast cancer patients treated with neoadjuvant chemotherapy. METHODS: A total of 127 breast cancer patients were treated with neoadjuvant chemotherapy every 2 weeks as part of 2 studies. Study A consisted of the administration of Adriamycin (40 mg/m(2)) on day 1 plus paclitaxel (150 mg/m(2)) and gemcitabine 2000 mg/m(2)) on day 2 for 6 cycles (n = 54). Study B consisted of the administration of epirubicin (90 mg/m(2)), cyclophosphamide (600 mg/m(2)) on day 1 for 3 cycles, followed by the administration of paclitaxel (150 mg/m(2)) and gemcitabine 2500 (mg/m(2)) on day 1 with or without trastuzumab according to HER2 status (n = 73). In study A, patients did not receive trastuzumab regardless of HER2 status. The molecular subtypes of the patients with breast cancer were classified as 49% HR(+)/HER2(-), 17.5% HR(+)/HER2(+), 13.5% HR(-)/HER2(+), and 20% HR(-)/HER2(-). RESULTS: Pathologic complete response (pCR), defined as the absence of invasive cells in the breast and the lymph nodes, was achieved in 35 (28%) patients. The pCR rate was significantly different between the molecular subtypes of breast cancer, with 9% in HR(+)/HER2(-), 23% in HR(+)/HER2(+), 50% in HR(-)/HER2(+), and 56% in HR(-)/HER2(-) tumors (P < .001). The pCR rate was significantly higher in tumors that had high Ki-67 (≥20%) expression and were HR(-). HER2(+) was associated with a higher trend of pCR but did not reach statistical significance. The median follow-up was 81 months (r = 15-150 months). Patients who achieved a pCR had a significantly lower recurrence (P = .01) and higher overall survival (P = .02) compared with those who did not achieve pCR. A multivariate analysis revealed that pCR (hazard ratio 0.24 [95% CI, 0.07-0.7]; P = .019), the molecular subtype (hazard ratio 0.3 [95% CI, 0.1-0.8]; P = .02), and the Ki-67 index (hazard ratio 3.2 [95% CI, 1.4-7.1]; P = .004) were significant independent predictors of disease-free survival. Similar results were obtained for overall survival, in which the pCR rate (hazard ratio 0.119 [95% CI, 0.028-0.5]; P = .004), the molecular subtype (hazard ratio 0.17 [95% CI, 0.03-0.86]; P = .02), and the Ki-67 index (hazard ratio 3.6 [95% CI, 1.3-9.7]; P = .01) also displayed a significant influence on survival. CONCLUSIONS: Molecular subtypes and Ki-67 index were independent prognostic factors for disease-free survival and overall survival in breast cancer patients treated with neoadjuvant chemotherapy. A high rate of Ki-67 and HR(-) expression were predictors of pCR. SN - 1938-0666 UR - https://www.unboundmedicine.com/medline/citation/23318089/The_role_of_immunohistochemistry_in_breast_cancer_patients_treated_with_neoadjuvant_chemotherapy:_an_old_tool_with_an_enduring_prognostic_value_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1526-8209(12)00265-0 DB - PRIME DP - Unbound Medicine ER -