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ER, PgR, Ki67, p27(Kip1), and histological grade as predictors of pathological complete response in patients with HER2-positive breast cancer receiving neoadjuvant chemotherapy using taxanes followed by fluorouracil, epirubicin, and cyclophosphamide concomitant with trastuzumab.

Kurozumi S, Inoue K, Takei H, Matsumoto H, Kurosumi M, Horiguchi J, Takeyoshi I, Oyama T - BMC Cancer (2015)

Bottom Line: A high pathological complete response (pCR) rate has been achieved using this regimen; however, the predictive factors and prognostic effects of pCR currently remain unclear.RFS was significantly better in the pCR group than in the non-pCR group (p = 0.018).Patients with remaining nodal disease in the pCR group had worse OS (p = 0.0002).

View Article: PubMed Central - PubMed

Affiliation: Division of Breast Surgery, Saitama Cancer Center, Saitama, Japan. chachagot-a-mail@hotmail.co.jp.

ABSTRACT

Background: Neoadjuvant chemotherapy (NAC) with taxanes followed by fluorouracil, epirubicin, and cyclophosphamide (FEC), and concurrent trastuzumab is a potent regimen for HER2 over-expressing breast cancer. A high pathological complete response (pCR) rate has been achieved using this regimen; however, the predictive factors and prognostic effects of pCR currently remain unclear. In the present study, we determined whether pCR was related to histological grade (HG) and several biological factors including p27(Kip1). We also assessed the prognosis of the pCR and non-pCR groups, and expected differences between those positive and negative for lymph node metastasis after chemotherapy.

Methods: A total of 129 Japanese women with HER2-positive invasive breast cancer received either paclitaxel or docetaxel followed by FEC, with the concomitant administration of trastuzumab. The statuses of HG, ER, PgR, Ki67, and p27(Kip1) were evaluated to determine their relationship with pCR. Relapse-free survival (RFS) and overall survival (OS) were also analyzed for their relationship with pCR and pathological nodal involvement.

Results: pCR was obtained in 84 out of 129 patients and the pCR rate was 65.1%. The pCR rates related to 5 factors were as follows: HG (grade 3, 70.0% vs. grades 1-2, 36.8%), ER (negative, 78.6% vs. positive, 40.0%), PgR (negative, 75.3% vs. positive, 38.9%), Ki67 (high, 72.0% vs. low, 47.2%), and p27(Kip1) (low, 71.0% vs. high, 50.0%). RFS was significantly better in the pCR group than in the non-pCR group (p = 0.018). Patients with remaining nodal disease in the pCR group had worse OS (p = 0.0002).

Conclusions: High-HG, low-ER, low-PgR, high-Ki67, and low-p27(Kip1) were identified as predictive factors of pCR in NAC with trastuzumab, while pCR and negative nodes were predictive of better survivals.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemical findings of p27Kip1.a Nuclei of cancer cells showing highly positive immunoreactions for p27Kip1. b The cytoplasm of cancer cells was weakly positive, whereas the nuclei were negative for p27Kip1
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Fig1: Immunohistochemical findings of p27Kip1.a Nuclei of cancer cells showing highly positive immunoreactions for p27Kip1. b The cytoplasm of cancer cells was weakly positive, whereas the nuclei were negative for p27Kip1

Mentions: The expression of ER, PgR, and HER2 proteins was examined by immunohistochemistry and HER2 gene amplification was evaluated by fluorescence in situ hybridization (FISH) using specimens obtained by needle biopsy as a routine practice before NAC. On the other hand, the expression of Ki67 and p27Kip1 was retrospectively examined by immunohistochemistry using needle biopsy specimens as part of this study. Primary antibody sources were as follows: ER (1D5, DAKO, Denmark), PgR (PgR636, DAKO, Denmark), HER2 (HercepTest, DAKO, Denmark), Ki67 (MIB-1, DAKO, Denmark), and p27Kip1 (Santa Cruz Biotechnology, USA). Positive ER and PgR statuses were defined by the presence of 1 % or more positive nuclei. A high Ki-67 LI and strong expression of p27Kip1 were defined by the presence of 30 % and 75 % or more positive nuclei, respectively (Fig. 1a). Cancer cells that positively expressed p27Kip1 in the cytoplasm were categorized as “negative” (Fig. 1b). The ER status (positive vs. negative), PgR status (positive vs. negative), Ki67 LI (high vs. low), and p27Kip1 expression (high vs. low) at baseline were analyzed for their relationships with pCR.Fig. 1


ER, PgR, Ki67, p27(Kip1), and histological grade as predictors of pathological complete response in patients with HER2-positive breast cancer receiving neoadjuvant chemotherapy using taxanes followed by fluorouracil, epirubicin, and cyclophosphamide concomitant with trastuzumab.

Kurozumi S, Inoue K, Takei H, Matsumoto H, Kurosumi M, Horiguchi J, Takeyoshi I, Oyama T - BMC Cancer (2015)

Immunohistochemical findings of p27Kip1.a Nuclei of cancer cells showing highly positive immunoreactions for p27Kip1. b The cytoplasm of cancer cells was weakly positive, whereas the nuclei were negative for p27Kip1
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4562359&req=5

Fig1: Immunohistochemical findings of p27Kip1.a Nuclei of cancer cells showing highly positive immunoreactions for p27Kip1. b The cytoplasm of cancer cells was weakly positive, whereas the nuclei were negative for p27Kip1
Mentions: The expression of ER, PgR, and HER2 proteins was examined by immunohistochemistry and HER2 gene amplification was evaluated by fluorescence in situ hybridization (FISH) using specimens obtained by needle biopsy as a routine practice before NAC. On the other hand, the expression of Ki67 and p27Kip1 was retrospectively examined by immunohistochemistry using needle biopsy specimens as part of this study. Primary antibody sources were as follows: ER (1D5, DAKO, Denmark), PgR (PgR636, DAKO, Denmark), HER2 (HercepTest, DAKO, Denmark), Ki67 (MIB-1, DAKO, Denmark), and p27Kip1 (Santa Cruz Biotechnology, USA). Positive ER and PgR statuses were defined by the presence of 1 % or more positive nuclei. A high Ki-67 LI and strong expression of p27Kip1 were defined by the presence of 30 % and 75 % or more positive nuclei, respectively (Fig. 1a). Cancer cells that positively expressed p27Kip1 in the cytoplasm were categorized as “negative” (Fig. 1b). The ER status (positive vs. negative), PgR status (positive vs. negative), Ki67 LI (high vs. low), and p27Kip1 expression (high vs. low) at baseline were analyzed for their relationships with pCR.Fig. 1

Bottom Line: A high pathological complete response (pCR) rate has been achieved using this regimen; however, the predictive factors and prognostic effects of pCR currently remain unclear.RFS was significantly better in the pCR group than in the non-pCR group (p = 0.018).Patients with remaining nodal disease in the pCR group had worse OS (p = 0.0002).

View Article: PubMed Central - PubMed

Affiliation: Division of Breast Surgery, Saitama Cancer Center, Saitama, Japan. chachagot-a-mail@hotmail.co.jp.

ABSTRACT

Background: Neoadjuvant chemotherapy (NAC) with taxanes followed by fluorouracil, epirubicin, and cyclophosphamide (FEC), and concurrent trastuzumab is a potent regimen for HER2 over-expressing breast cancer. A high pathological complete response (pCR) rate has been achieved using this regimen; however, the predictive factors and prognostic effects of pCR currently remain unclear. In the present study, we determined whether pCR was related to histological grade (HG) and several biological factors including p27(Kip1). We also assessed the prognosis of the pCR and non-pCR groups, and expected differences between those positive and negative for lymph node metastasis after chemotherapy.

Methods: A total of 129 Japanese women with HER2-positive invasive breast cancer received either paclitaxel or docetaxel followed by FEC, with the concomitant administration of trastuzumab. The statuses of HG, ER, PgR, Ki67, and p27(Kip1) were evaluated to determine their relationship with pCR. Relapse-free survival (RFS) and overall survival (OS) were also analyzed for their relationship with pCR and pathological nodal involvement.

Results: pCR was obtained in 84 out of 129 patients and the pCR rate was 65.1%. The pCR rates related to 5 factors were as follows: HG (grade 3, 70.0% vs. grades 1-2, 36.8%), ER (negative, 78.6% vs. positive, 40.0%), PgR (negative, 75.3% vs. positive, 38.9%), Ki67 (high, 72.0% vs. low, 47.2%), and p27(Kip1) (low, 71.0% vs. high, 50.0%). RFS was significantly better in the pCR group than in the non-pCR group (p = 0.018). Patients with remaining nodal disease in the pCR group had worse OS (p = 0.0002).

Conclusions: High-HG, low-ER, low-PgR, high-Ki67, and low-p27(Kip1) were identified as predictive factors of pCR in NAC with trastuzumab, while pCR and negative nodes were predictive of better survivals.

No MeSH data available.


Related in: MedlinePlus