Tumor necrosis is a prognostic predictor for early recurrence and death in lymph node-positive breast cancer: a 10-year follow-up study of 728 Eastern Cooperative Oncology Group patients.

Gilchrist, Kennedy W.; Gray, R; Fowble, Barbara; Tormey, Douglas C.; th, S G Taylor

doi:10.1200/jco.1993.11.10.1929

Cited by 113 publications

(87 citation statements)

References 33 publications

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“…Although the current prognostic factors predict relapse in the first 5 years after therapy, it is unclear whether these parameters are useful in predicting long-term survival or late relapse. [28][29][30] It has been hypothesized that immunologic factors, specifically T regs , play a significant role in tumor development and progression due to their ability to induce immune tolerance to a cancer. Given their possible role in tumor progression, T regs are increasingly being looked at as both prognostic factors and therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

Immunosuppressive regulatory T cells are associated with aggressive breast cancer phenotypes: a potential therapeutic target

2008

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FoxP3 is a marker for immunosuppressive CD25 þ CD4 þ regulatory T cells. These regulatory T cells are thought to play a role in inducing immune tolerance to antigens and may be selectively recruited by carcinomas. We investigated whether breast carcinomas had significant numbers of FoxP3-positive regulatory T cells by immunohistochemistry, and if their presence was associated with other prognostic factors, such as Nottingham grade, hormone receptor immunohistochemical profile, tumor size, or lymph node metastases. Ninety-seven needle core or excisional breast biopsies with invasive breast carcinoma diagnosed at the University of Washington were stained with antibodies to FoxP3, estrogen receptor, and Her2/neu. The numbers of FoxP3-positive cells present within the neoplastic epithelium, and immediately adjacent stroma were counted manually in three high-powered fields (HPFs; Â 400) by two independent pathologists. The average scores were then correlated with the parameters of interest. A threshold of Z15 FoxP3-positive cells/HPF was used to define a FoxP3-positive case in some analyses. Higher average numbers of FoxP3-positive cells present significantly correlated with higher Nottingham grade status (P ¼ 0.000229). In addition, the presence of significant numbers (Z15/HPF) of FoxP3-positive cells in breast carcinoma was positively associated with higher Nottingham grade (P ¼ 0.00002585). Higher average numbers of FoxP3-positive cells were also significantly associated with larger tumor size (42.0 cm; P ¼ 0.012824) and trended toward an association with estrogen receptor negativity. Interestingly, 'triple-negative' (estrogen and progesterone receptor negative and Her2/neu negative) Nottingham grade III cases were also significantly associated with high numbers of FoxP3 cells. These results argue that regulatory T cells may play a role in inducing immune tolerance to higher grade, more aggressive breast carcinomas, and are a potential therapeutic target for these cancers.

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Section: Discussionmentioning

confidence: 99%

Immunosuppressive regulatory T cells are associated with aggressive breast cancer phenotypes: a potential therapeutic target

2008

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“…The 5-year DFS ranges from 17 to 56% (weighted average 38%). [6][7][8][26][27][28][29][30][31][32][33][34][35][36][37][38] Four trials have been published using HDCT/PSC as treatment for stage II and/or IIIA patients with у10 nodes. [6][7][8]39,40 The 5-year DFS with HDCT is substantially better (range 50-64%, weighted average 58%) compared to patients receiving conventionaldose adjuvant chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…HDCT trials in patients with у10 nodes do not select more hormone receptor-positive patients (range, 56-67%; weighted mean, 61%) (Refs 6, 8, 40 and the current series) than conventional-dose chemotherapy trials in the same group (range, 42-74%; weighted mean, 58%). 6,8,[28][29][30][32][33][34][35][36][37][38] Sixty-two percent of 479 patients undergoing HDCT and reported to the Autologous Blood and Marrow Transplant Registry (ABMTR) were ER positive. 44 Several conventional-dose chemotherapy studies in у10 nodes utilized tamoxifen after adjuvant chemotherapy with 5-year DFS of 17-56% (weighted average, 32%), 6,7,[28][29][30]35,36,38 results still inferior to HDCT trials utilizing tamoxifen (Refs 6, 7, 39, 40 and the current series).…”

Section: Discussionmentioning

confidence: 99%

High-dose chemotherapy (CTM) for breast cancer

Wolf

Rugo

et al. 2000

Bone Marrow Transplant

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Summary:We designed and implemented a new mitoxantronebased high-dose chemotherapy regimen to minimize pulmonary injury (seen in carmustine-based regimens) in patients with breast cancer. One hundred and ninetyone breast cancer patients (99 stage II/IIIA; 27 stage IIIB; 65 stage IV responsive to conventional-dose chemotherapy) were treated with high-dose chemotherapy (CTM) delivered over 4 days (cyclophosphamide (6 g/m 2 ), thiotepa (600 mg/m 2 ), and mitoxantrone (24-60 mg/m 2 )) followed by autologous hematopoietic stem cell rescue. Stage II/III patients received chest wall radiation and tamoxifen (if hormone-receptor positive) after CTM. The 5-year event-free survival (EFS) for stage II/IIIA patients with 10 or more involved axillary lymph nodes (n = 80) was 62 ؎ 12%. Hormone receptor-positive patients with 10 or more nodes did significantly better than negative patients. The EFS for stage IIIB patients at 5 years was 44 ؎ 19%; for stage IV patients at 5 years was 17 ؎ 10%. Stage IV patients achieving complete response in viscera and/or soft tissue prior to CTM did significantly better than those achieving a partial response. There were six (3%) treatment-related deaths including two due to diffuse alveolar hemorrhage. There were no episodes of delayed interstitial pneumonitis. There were six severe cardiac events in 91 patients (6.6%) but none after instituting mitoxantrone dose-adjustment in the final 100 patients. We conclude that CTM is associated with a low treatment-related mortality and little pulmonary toxicity. CTM produces excellent outcomes in stage II/IIIA patients with 10 or more involved axillary lymph nodes. Bone Marrow Transplantation (2000) 26, 257-268.

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“…There are many studies that show differences between the prognostic parameters of the primary-invasive tumours of invasive ductal carcinoma (IDC) patients with and without nodal metastasis (Gilchrist et al, 1993;Pedersen et al, 2000;Depowski et al, 2001;Scorilas et al, 2001), and the former show a significantly worse prognostic course than the latter. Thus, it is necessary to accurately predict the difference in the malignant potential of IDCs with and without nodal metastasis from the viewpoint of neoadjuvant or adjuvant chemotherapy for IDC patients.…”

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confidence: 99%

Primary tumour–vessel tumour–nodal tumour classification for patients with invasive ductal carcinoma of the breast

et al. 2005

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There are many studies that show biological differences between invasive ductal carcinoma (IDC) with and without nodal metastasis, but no prognostic classification taking into consideration any biological differences between them is currently available. We previously investigated the histological characteristics that play an important role in tumour progression of IDCs according to their nodal status, and a new prognostic histological classification, the primary tumour -vessel tumour -nodal tumour (PVN) classification, was devised based on the histological characteristics of IDCs with and without nodal metastasis. Multivariate analyses using the Cox proportional hazard regression models were used to compare the ability of the PVN classification to predict tumour recurrence and death in 393 IDC patients based on the following histological classifications: (1) the pTNM classification, (2) the Nottingham Prognostic Index, (3) the modified Nottingham Prognostic Index, and (4) the histologic grade. In IDCs without nodal metastasis, only the PVN classification significantly increased the hazard rates (HRs) of tumour recurrence and death (Po0.05), independent of the hormone receptor status. Similarly, in IDCs with nodal metastases, only the PVN classification significantly increased the HRs of tumour recurrence and death (Po0.05), independent of the hormone receptor status. We conclude that the PVN prognostic histological classification is the best classification available for IDC of the breast. British Journal of Cancer (2005) There are many studies that show differences between the prognostic parameters of the primary-invasive tumours of invasive ductal carcinoma (IDC) patients with and without nodal metastasis (Gilchrist et al, 1993;Pedersen et al, 2000;Depowski et al, 2001;Scorilas et al, 2001), and the former show a significantly worse prognostic course than the latter. Thus, it is necessary to accurately predict the difference in the malignant potential of IDCs with and without nodal metastasis from the viewpoint of neoadjuvant or adjuvant chemotherapy for IDC patients.We recently clearly demonstrated that the histological characteristics of tumour cells in lymph vessels, blood vessels, and lymph nodes play a very important role in tumour progression of IDCs of the breast (Hasebe et al, 2002b(Hasebe et al, , 2003a(Hasebe et al, , b, 2004a. Among these histological characteristics, we clearly identified the most important histological characteristics predicting the outcome of IDC patients with and without nodal metastasis (Hasebe et al, 2004b). Our studies clearly showed that the prognostic histological characteristics of primary-invasive tumours and tumour cells in vessels differ in IDCs without and with nodal metastasis, and that the histological characteristics of tumours in lymph nodes play a more important role in the outcomes of IDC patients with nodal metastasis than those of the primary-invasive tumours or tumour cells in vessels. These findings strongly suggest the characteristics of IDCs with and witho...

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Tumor necrosis is a prognostic predictor for early recurrence and death in lymph node-positive breast cancer: a 10-year follow-up study of 728 Eastern Cooperative Oncology Group patients.

Abstract: Confluent TN of any dimension in invasive areas of lymph node-positive breast cancer is an independent predictor for early recurrence and death from the disease.

Cited by 113 publications

References 33 publications

Immunosuppressive regulatory T cells are associated with aggressive breast cancer phenotypes: a potential therapeutic target

Immunosuppressive regulatory T cells are associated with aggressive breast cancer phenotypes: a potential therapeutic target

High-dose chemotherapy (CTM) for breast cancer

Primary tumour–vessel tumour–nodal tumour classification for patients with invasive ductal carcinoma of the breast

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