Molecular markers for prognosis after isolated postmastectomy chest wall recurrence

Haffty, Bruce G.; Hauser, Analene; Choi, Doo Ho; Parisot, B S Nicole; Rimm, David L.; King, Bonnie L.; Carter, Darryl

doi:10.1002/cncr.11915

Cited by 44 publications

(36 citation statements)

References 41 publications

(80 reference statements)

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“…DAKO 3,3-diaminobenzidine tetrahydrochloride dehydrate was then applied as a chromogenic substrate. Tissue microarrays were also stained for HER-2/neu, estrogen receptor, and progesterone receptor from a previous study (33).…”

Section: Methodsmentioning

confidence: 99%

Cyclooxygenase-2 Expression in Postmastectomy Chest Wall Relapse

Kim¹,

Bossuyt²,

Ponn

et al. 2005

Clinical Cancer Research

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Purpose: Cyclooxygenase-2 (COX-2) expression has been shown to be associated with radiation resistance, which theoretically could be overcome with the use of COX-2 inhibitors. The purpose of this study was to assess the prognostic significance and clinical correlations of COX-2 expression (COX) in a cohort of patients treated with radiation for postmastectomy chest wall relapse. Experimental Design: Between 1975 and 1999, 113 patients were treated for isolated postmastectomy chest wall relapse. All patients were treated with biopsy and/or excision of the chest wall recurrence followed by radiation therapy. Median follow-up was 10 years. All clinical data, including demographics, pathology, staging, receptor status, HER-2/neu status, and adjuvant therapy, were entered into a computerized database. Paraffin-embedded chest wall recurrence specimens were retrieved from 42 patients, of which 38 were evaluated, created into a tissue microarray, stained by immunohistochemical methods for COX, and graded 0 to 3+. A score of 2 to 3+ was considered positive. Results: Overall survival from original diagnosis for entire cohort was 44% at 10 years. Survival rate after chest wall recurrence was 28% at 10 years.The distant metastasis-free survival rate after chest wall recurrence was 40% at10 years. Local-regional control of disease was achieved in 79% at 10 years after chest wall recurrence. COX was considered positive in 13 of 38 cases. COX was inversely correlated with estrogen receptor (P = 0.045) and progesterone receptor (P = 0.028), and positively correlated with HER-2/neu (P = 0.003). COX was also associated with a shorter time to postmastectomy chest wall relapse. The distant metastasis-free rate for COX-negative patients was 70% at 10 years, compared with 31% at 10 years for COX-2^positive patients (P = 0.029). COX positive had a poorer local-regional progression-free rate of 19% at 10 years, compared with 81% at 10 years for COX negative. This was of high statistical significance with a P value of 0.003. Conclusions: Outcome following radiation therapy for postmastectomy chest wall relapse is relatively poor. Positive COX correlated with other markers of poor outcome, including a shorter time to local relapse, negative estrogen receptor/progesterone receptor, and positive Her-2/neu status. Positive COX correlated with higher distant metastasis and lower local-regional control of disease. If confirmed with larger studies, these data have implications with respect to the concurrent use of COX-2 inhibitors and radiation for postmastectomy chest wall relapse.Despite the increasing use of breast-conserving surgeries for breast cancer, mastectomy still plays a large role in primary and salvage treatment. Unfortunately, despite the attempted removal of all breast tissue during a mastectomy, local-regional recurrences still occur. About 10% to 20% of all patients develop a local recurrence, mostly within the boundaries of the chest wall, within a 10-year period despite achieving negative surgical margins (1 -8). Pr...

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Section: Methodsmentioning

confidence: 99%

Cyclooxygenase-2 Expression in Postmastectomy Chest Wall Relapse

Kim¹,

Bossuyt²,

Ponn

et al. 2005

Clinical Cancer Research

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“…As previously described, this 2-fold redundancy has been validated and correlates highly with whole-section staining (15)(16)(17). Five-micrometer sections were cut with a tape-based tissue transfer system (Intrumedics) and processed as described previously (15)(16)(17).…”

Section: Clinical Specimens Tissue Microarrays and Pathology Evaluamentioning

confidence: 95%

“…Five-micrometer sections were cut with a tape-based tissue transfer system (Intrumedics) and processed as described previously (15)(16)(17).…”

Section: Clinical Specimens Tissue Microarrays and Pathology Evaluamentioning

confidence: 99%

The Proapoptotic Molecule BLID Interacts with Bcl-XL and Its Downregulation in Breast Cancer Correlates with Poor Disease-Free and Overall Survival

Broustas

Ross

Yang

et al. 2010

Clinical Cancer Research

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Purpose: BLID is a BH3-like motif containing apoptotic member of the Bcl-2 family of proteins. This study was designed to investigate the mechanism of BLID-induced apoptosis and to assess the significance of BLID expression in breast cancer.Experimental Design: The interaction between BLID and Bcl-X L was examined using in vitro transcription/translation, coimmunoprecipitation, and immunoflourescence assays. The relationship between BLID mRNA expression and pathologic measures in breast cancer specimens (n = 55) was examined using the publicly available ONCOMINE microarray database. Immunohistochemistry was done using formalinfixed, paraffin-embedded sections of 148 cases of invasive ductal breast carcinomas (IDC) and 58 cases of invasive lobular breast carcinomas, and breast tissue microarrays representing additional 437 cases (>85% IDC) with associated clinicopathologic database and long-term clinical follow-up (median 7 years).Results: BLID was found to interact with Bcl-X L , and the binding was enhanced in cancer cells exposed to doxorubicin or cisplatin. Exogenous expression of BLID correlated with activation of Bax and an increase in cytosolic cytochrome c. BLID mRNA expression was significantly reduced in grade 3 relative to grade 1 and 2 breast cancer (P = 0.023). Cytoplasmic BLID immunoreactivity was absent in IDC compared with invasive lobular breast carcinoma (P < 0.001). Lack of BLID expression was associated with younger age (median 40 years), African American ethnicity, tumor size, and triple-negative breast cancer (estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 negative; all P < 0.005). Significant correlations were observed between BLID negativity and declines in overall, cause-specific, and local relapse-free survival (all P < 0.03). Multivariate analysis indicated that BLID is an independent prognostic factor of distant metastasis-free survival (hazard ratio, 0.302; 95% confidence interval, 0.160-0.570, P = 0.0002).Conclusion: BLID is a new binding partner of Bcl-X L and a significant prognostic factor in breast cancer. Clin Cancer Res; 16(11); 2939-48. ©2010 AACR.The Bcl-2 family of proteins plays a pivotal role in the control of cell death and response of cancer cells to antineoplastic drugs and γ-radiation (1, 2). The antiapoptotic members (e.g., Bcl-2, Bcl-X L , Mcl-1) share homology within three or four BH (Bcl-2 homology) domains (BH 1-4). The proapoptotic proteins contain either two or three BH domains (e.g., Bax, Bak) or only the short (9-16 amino acids) BH3 domain (BH3-only proteins, e.g., Bad, Puma, Noxa; ref. 3). Under unstimulated conditions, Bax and Bak are sequestered by one or more prosurvival members. Numerous landmark studies have shown that binding of a BH3-only apoptotic molecule to an antiapoptotic member is a critical step in the activation of Bax/Bak, release of cytochrome c, and activation of caspase-9 and caspase-3 (4, 5). More recently, a new class of proapoptotic molecules has emerged that contains a B...

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“…HER2 status is a significant prognostic factor for local-regional disease progression. Patients with positive HER2 status had a local-regional disease progressionfree rate of 59% compared with 92% for patients with negative HER2 status (Haffty et al, 2004). Although the application of monoclonal antibody against HER2 -trastuzumab showed beneficial effect when combined with docetaxel and platinum salts (Pegram et al, 2004) or paclitaxel and carboplatin (Perez et al, 2005;Robert et al, 2006), its use beyond first-line therapy might develop resistance to this agent.…”

Section: Therapy Of Her2 Positive Breast Cancersmentioning

confidence: 99%