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Activated Caspase 3 Expression in Remnant Disease After Neoadjuvant Chemotherapy May Predict Outcomes of Breast Cancer Patients

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

A number of studies have indicated that patients obtaining a pathological complete response (pCR) from neoadjuvant chemotherapy (NAC) have a good prognosis; however, prognostic factors for non-pCR patients are not yet well-established. By examining remnant cancer in non-pCR patients, the expression of cleaved Caspase 3 (Casp3), an activated apoptotic marker, was immunohistochemically investigated to determine whether this protein has the potential to serve as a novel marker for predicting patient outcomes.

Methods

We investigated 218 patients with invasive breast cancer who received NAC and underwent surgery during the 2006 through 2008 period at our institution. Following surgery, standard adjuvant endocrine therapy was administered if a tumor was hormone receptor-positive. Casp3 was evaluated in remnant cancer based on the number of positive cells in five high-power fields.

Results

pCR was obtained in 49 patients, and 50 of the 169 non-pCR patients developed recurrences during the median 82-month observation period. We found large tumor size, lymph node involvement, lymph vessel invasion, estrogen receptor-negative, progesterone receptor-negative, high Ki67 and high Casp3 expression to be factors related to tumor recurrence. A logistic regression model revealed that lymph node involvement, as well as high Ki67 and Casp3, to be factors independently predicting recurrence, while lymph vessel invasion and high Ki67 expression were found to be related to breast cancer mortality.

Conclusions

Patients with remnant cancer showing high Casp3 expression had poor outcomes. Our results showed that Casp3 is a potential prognostic marker for non-pCR patients.

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Acknowledgment

The authors sincerely appreciate the efforts of Ms. Naomi Kadowaki, Department of Pathology and Oncology, Juntendo University School of Medicine, for her advice on the Casp3 immunohistochemistry.

Conflicts of interest

Takanori Himuro, Yoshiya Horimoto, Atsushi Arakawa, Joe Matsuoka, Emi Tokuda, Masahiko Tanabe, and Mitsue Saito have no conflicts of interest to declare.

Author information

Authors and Affiliations

  1. Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan

    Takanori Himuro MD, Yoshiya Horimoto MD, PhD, Emi Tokuda MD, PhD, Masahiko Tanabe MD, PhD & Mitsue Saito MD, PhD

  2. Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, Japan

    Yoshiya Horimoto MD, PhD

  3. Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan

    Atsushi Arakawa MD, PhD

  4. Clinical Research Support Center, Juntendo University School of Medicine, Tokyo, Japan

    Joe Matsuoka MS

Authors
  1. Takanori Himuro MD
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  2. Yoshiya Horimoto MD, PhD
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  3. Atsushi Arakawa MD, PhD
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  4. Joe Matsuoka MS
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  5. Emi Tokuda MD, PhD
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  6. Masahiko Tanabe MD, PhD
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  7. Mitsue Saito MD, PhD
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Corresponding author

Correspondence to Yoshiya Horimoto MD, PhD.

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Supplementary Fig. 1

The median number of Casp3-positive cells in five HPF was 4 in the remnant disease specimens of the 157 patients (dotted line). Patients with recurrences are indicated in red. Supplementary material 1 (DOCX 20 kb)

Supplementary Fig. 2

Casp3 expressions before and after NAC from 24 cases who showed the highest Casp3 in surgical specimens are shown. There was no significant difference between biopsy and surgical specimens, with the mean numbers of Casp3-positive cells being 65 and 71, respectively. Supplementary material 2 (PPTX 65 kb)

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Himuro, T., Horimoto, Y., Arakawa, A. et al. Activated Caspase 3 Expression in Remnant Disease After Neoadjuvant Chemotherapy May Predict Outcomes of Breast Cancer Patients. Ann Surg Oncol 23, 2235–2241 (2016). https://doi.org/10.1245/s10434-016-5164-9

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  • DOI: https://doi.org/10.1245/s10434-016-5164-9

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