scholarly journals Abstract 1046: Developing patient-derived xenograft tumor models that recapture clinical manifestation of inflammatory breast cancer patients

Author(s):  
Wenan Qiang ◽  
Youbin Zhang ◽  
Demirkan Gursel Gursel ◽  
Jian-Jun Wei ◽  
Charles David James ◽  
...  
Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 259
Author(s):  
Madhuchhanda Kundu ◽  
Sumita Raha ◽  
Avik Roy ◽  
Kalipada Pahan

Although some therapies are available for regular breast cancers, there are very few options for triple-negative breast cancer (TNBC). Here, we demonstrated that serum level of IL-12p40 monomer (p40) was much higher in breast cancer patients than healthy controls. On the other hand, levels of IL-12, IL-23 and p40 homodimer (p402) were lower in serum of breast cancer patients as compared to healthy controls. Similarly, human TNBC cells produced greater level of p40 than p402. The level of p40 was also larger than p402 in serum of a patient-derived xenograft (PDX) mouse model. Accordingly, neutralization of p40 by p40 mAb induced death of human TNBC cells and tumor shrinkage in PDX mice. While investigating the mechanism, we found that neutralization of p40 led to upregulation of human CD4+IFNγ+ and CD8+IFNγ+ T cell populations, thereby increasing the level of human IFNγ and decreasing the level of human IL-10 in PDX mice. Finally, we demonstrated the infiltration of human cytotoxic T cells, switching of tumor-associated macrophage M2 (TAM2) to TAM1 and suppression of transforming growth factor β (TGFβ) in tumor tissues of p40 mAb-treated PDX mice. Our studies identify a possible new immunotherapy for TNBC in which p40 mAb inhibits tumor growth in PDX mice.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11062-e11062
Author(s):  
Saeed Rafii ◽  
Christopher John Poole ◽  
Adele Francis ◽  
Shalini Chaudhri ◽  
Daniel Rea

e11062 Background: Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer characterised by rapidly progressive breast erythema, pain and tenderness, oedema and paeu d’orange. It is estimated that between 1-4 % of all newly diagnosed breast cancer patients in the United Kingdom have IBC. Methods: We retrospectively identified 51 patients who were treated for IBC at 7 hospitals in the West midlands area of the United Kingdom between 1997 and 2011. Data including patients’ demographics, clinical, radiological and histopathological characteristics were collected from electronic clinical records. The test for HER-2 over-expression was not carried out routinely before 2002, therefore HER-2 status of such patients were assessed retrospectively on the archived tissues. A cox regression analysis was used for statistical assessment of survival and prognostic factors. Results: Median age at diagnosis was 55 years (range 34-83 yrs). Median overall (OS) and progression free survival (PFS) were 32 months (range 7-97 months) and 27 months (range 2-53 months) respectively. The 3–year survival rate for the entire cohort was 32%. Majority of patients were ER and HER-2 positive (49% and 52% respectively). The rate of complete pathological response (pCR) after neoadjuvant chemotherapy was 14%. All cases who had achieved pCR were HER-2 positive who had received anti HER-2 treatment during the neoadjuvant chemotherapy. The OS for the HER-2 positive patients with pCR was not statistically different from the whole cohort (49 vs 32 months, p=0.09) or from the patients with residual disease (49 vs 26 months, p=0.13). Although the triple negative IBC patients consisted 20% of the cohort, no patients in this group had achieved pCR. The OS and PFS for the triple negative patients were 20 and 14 months respectively. Although the rate of pCR was higher in patients treated with taxane compared to those treated with anthracycline containing chemotherapy (35% vs 7%), there was no significant difference in OS between either of these regimens (29 vs 27 months). Conclusions: HER-2 positive IBC patients had higher rate of achieving pCR after neo-adjuvant anti HER-2 therapy. However higher rate of pCR did not improve the OS.


1998 ◽  
Vol 16 (12) ◽  
pp. 3731-3735 ◽  
Author(s):  
S Chang ◽  
A U Buzdar ◽  
S D Hursting

PURPOSE No studies have investigated the etiology of inflammatory breast cancer (IBC), the most lethal form of breast cancer. Because high body mass index (BMI) is associated with decreased risk of premenopausal breast cancer but increased risk of postmenopausal breast cancer, we evaluated whether high BMI was a risk factor for IBC. PATIENTS AND METHODS In a case-comparison study, we matched by ethnicity and registration date 68 IBC patients treated at The University of Texas M.D. Anderson Cancer Center from 1985 to 1996 with 143 patients with non-IBC and 134 patients with cancer at sites other than the breast or reproductive tract (non-breast cancer). The non-breast cancer group was used in lieu of a population-based, healthy control group, which was not available. RESULTS IBC patients were younger at menarche and the time of their first live birth than non-IBC and non-breast cancer patients. The proportion of premenopausal IBC patients was higher than the proportion of premenopausal women in the comparison groups, although differences were not significant. There were no differences in height, but IBC patients were heavier (77.6 kg) than non-IBC (70.0 kg) and non-breast cancer patients (68.0 kg). After adjusting for other factors, women in the highest BMI tertile (BMI > 26.65 kg/m2) relative to the lowest tertile (BMI < 22.27) had significantly increased IBC risk (IBC v non-IBC, odds ratio [OR] = 2.45, 95% confidence interval [CI] = 1.05 to 5.73; IBC v non-breast cancer, OR = 4.52, 95% CI = 1.85 to 11.04). This association was not significantly modified by menopausal status and was independent of age at menarche, family history of breast cancer, gravidity, smoking status, and alcohol use. CONCLUSION Our investigation showed that high BMI was significantly associated with an increased risk of IBC. This association did not vary by menopausal status, although IBC patients were more likely to be premenopausal. Confirming our findings and identifying other IBC risk factors may provide directions for future research on the aggressive nature of IBC.


2011 ◽  
Vol 17 (5) ◽  
pp. 545-547 ◽  
Author(s):  
Brooke Spencer ◽  
Mousumi Banerjee ◽  
Sherif Omar ◽  
Hussein Khaled ◽  
Nayera Anwar ◽  
...  

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