Response to neo-adjuvant chemotherapy in women with BRCA1-positive breast cancers

Byrski, Tomasz; Gronwald, Jacek; Huzarski, Tomasz; Grzybowska, Ewa; Budryk, Magdalena; Stawicka, Małgorzata; Mierzwa, Tomasz; Szwiec, Marek; Wiśniowski, Rafał; Siołek, Monika; Narod, Steven A.; Lubiński, Jan

doi:10.1007/s10549-007-9600-1

Cited by 135 publications

(87 citation statements)

References 21 publications

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“…In a recent neoadjuvant trial of women with BRCA1 mutations and TNBC, almost 90% of patients had complete pathological responses to single agent cisplatin [18]. Results of a recent randomized phase Ⅱ study of the PARP (Poly (ADP-ribose) polymerase) inhibitor BSI-201 in combination with carboplatin and gemcitabine for metastatic TNBC, showed a significantly improved clinical benefit rate and, progression-free sur-…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological Characteristics of Basal Type Breast Cancer in Triple-Negative Breast Cancer

Kutomi¹,

Ohmura²,

Suzuki³

et al. 2012

JCT

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Background: Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor 2 (HER2) expression. Patients with TNBC derive no benefit from molecularly targeted treatments, such as endocrine therapy or trastuzumab, as they lack the appropriate targets for these drugs. TNBC is characterized by its biological aggressiveness and poor prognosis, and consists of two subtypes, basal and nonbasal. The purpose of our study is to differentiate the clinicopathological characteristics of the two subtypes. Methods: 367 patients with primary breast cancer were recruited from April 2004 to December 2010 at 1st Department of Surgery, Sapporo Medical University. ER, PgR, and HER2 status were evaluated in all cases. Moreover, we classified TNBC into basal, nonbasal subtypes on the basis of immunohistochemical staining of epidermal growth factor receptor (EGFR), cytokeratin (CK) 5/6. Basal type was defined as CK5/6-positive and/or EGFR-positive, and nonbasal type was defined as no expression of these two markers. Results: Breast cancer subtypes by molecular classification were Hormone receptor (HR)-positive/HER2-negative (61%), HR-positive/HER2-positive (10%), HR-negative/HER2-positive (14%), and HR-negative/HER2-negative (15%). There was no difference between the basal type and the nonbasal type in clinicopathological factors. But, the basal type was significantly associated with Ki67 labeling index (p = 0.0002), p53 expression (p = 0.047), and BRCA1 expression (p = 0.03). Further, patients with the basal type TNBC showed a shorter overall survival (p = 0.032) than did patients with the nonbasal type. Conclusion: Classification of TNBC subtypes by EGFR, CK5/6 is a very useful prognostic factor, and highlights the need for the development of an adequate new strategy for the basal type TNBC.

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Section: Discussionmentioning

confidence: 99%

Clinicopathological Characteristics of Basal Type Breast Cancer in Triple-Negative Breast Cancer

Kutomi¹,

Ohmura²,

Suzuki³

et al. 2012

JCT

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“…Furthermore, ten patients carrying BRCA1 mutation, with stages I to III breast cancer, who underwent platinum-based neoadjuvant therapy achieved 90% pathological complete response, therefore suggesting high effectiveness of this treatment in the BRCA1-defective setting. 27 In ovarian cancer, where platinum-based compounds are commonly included in conventional regimens, patients carrying BRCA1 or BRCA2 mutations had a genes with significant modulation generating a list of 172 genes that was submitted to the network-mapping tool, the Ingenuity Systems Software (Ingenuity Systems, Mountain View, CA). In this system the significance of the association between the data set and the canonical pathways was measured in two ways: (1) a ratio of the number of genes from the data set that map to the pathway divided by the total number of genes that map to the canonical pathway is displayed; (2) Fischer's exact test was used to calculate a p-value determining the probability that the association between the genes in the dataset and the canonical pathway is explained by chance alone.…”

Section: Methodsmentioning

confidence: 99%

Loss of BRCA1 function increases the antitumor activity of cisplatin against human breast cancer xenografts in vivo

Tassone¹,

Martino²,

Ventura³

et al. 2009

Cancer Biology & Therapy

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“…[16][17][18][19] Preclinical studies show that platinum-associated adducts block the transcriptional enzyme RNA polymerase II, causing transcriptional arrest, which leads to the ubiquitination and degradation of the large subunit of RNA polymerase II, thereby allowing access to DNA repair protein. 20 In clinical studies in patients with ovarian cancer, BRCA heterozygotes had a better response to platinum chemotherapy than women who had sporadic disease, which may have contributed to their improved survival. 18,21 Several retrospective and epidemiologic studies show that the TN phenotype of breast cancer is associated with a poorer prognosis and more aggressive clinical features than other subtypes.…”

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confidence: 99%

Treatment outcomes and clinicopathologic characteristics of triple‐negative breast cancer patients who received platinum‐containing chemotherapy

Uhm

Park

et al. 2008

Intl Journal of Cancer

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The aim of this study was to evaluate the role of platinum-containing chemotherapy for metastatic triple-negative breast cancer (TNBC) patients in terms of the response rate (RR) and progression-free survival. A second aim was to characterize the clinical behavior at the time of relapse of TNBC. We retrospectively analyzed the clinical outcomes of patients with metastatic breast cancer who received taxane-platinum chemotherapy as the first-or second-line treatment, focusing on the TN phenotype. In total, 257 patients with metastatic breast cancer received platinum-containing chemotherapy at Samsung Medical Center from 1999 to 2006. Of these patients, 106 patients with available data on estrogen (ER), progesterone (PgR) and human epidermal growth factor receptor-2 (HER2) receptor status received taxane-platinum regimen as the first-or second-line treatment. The overall RR of patients with TNBC was 39%. This rate did not differ significantly from those of patients with other phenotypes. The time to death after chemotherapy (19 vs. 50 months, p 5 0.037) and overall survival (OS) (21 vs. 56 months, p 5 0.030) differed significantly between patients with TNBC and non-TNBC. TNBC showed a unique locoregional infiltration pattern at relapse, which might reflect its aggressive clinical behavior. Despite the similar response to platinum-containing chemotherapy, patients with TNBC had a shorter OS than patients with non-TNBC. The implication of TN phenotype as poor prognostic factor is uncertain, because it needs to be defined whether poor outcome is related to the rapid growing characteristics of tumor itself or the resistance to drug therapy. Further prospective studies are warranted. ' 2008 Wiley-Liss, Inc.Key words: triple-negative breast cancer; platinum chemotherapy; BRCA1 Human breast cancer is a heterogeneous group of diseases, encompassing a number of distinct biological entities that differ in their behavior, outcome and response to therapy.1,2 DNA microarray analysis has revealed 5 subtypes of breast cancer: luminal A, luminal B, basal cell-like, human epidermal growth factor receptor-2 (HER2) positive and estrogen receptor (ER) negative, and normal-like. These subtypes have different prognoses and need different systemic treatment strategies.3,4 The basal cell-like tumors typically lack or show low expression of HER2 and ER, and exhibit a high expression level of genes characteristic of basal epithelial cells.1,4-7 These tumors might share many clinical and biologic behaviors with triple-negative breast cancers (TNBCs), which lack of expression of ER, progesterone receptor (PgR) and HER2. 5,8 However, although most basal cell-like cancers do not express ER, PgR or HER2, there is incomplete overlap between basal cell-like breast cancer and TNBC. 5,[8][9][10] The TN phenotype of breast cancer is characterized by more aggressive clinical behavior and poorer prognosis compared with the other subtypes, which likely reflect this subtype's high proliferative capacity and the lack of targeted therapies such as convent...

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Response to neo-adjuvant chemotherapy in women with BRCA1-positive breast cancers

Abstract: Breast cancers among BRCA1 carriers frequently do not exhibit sensitivity to docetaxel in the neo-adjuvant setting. It is likely that normal BRCA1 is required for clinical response to mitotic spindle poisons.

Cited by 135 publications

References 21 publications

Clinicopathological Characteristics of Basal Type Breast Cancer in Triple-Negative Breast Cancer

Clinicopathological Characteristics of Basal Type Breast Cancer in Triple-Negative Breast Cancer

Loss of BRCA1 function increases the antitumor activity of cisplatin against human breast cancer xenografts in vivo

Treatment outcomes and clinicopathologic characteristics of triple‐negative breast cancer patients who received platinum‐containing chemotherapy

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