Selected 2001 and 2000 Inflammatory Breast Cancer published research.
More recent research (2001) is at the top of the page, 2000 research is further down the page. Links to free full text (where available) will open in a new browser tab/window.
Shirakawa, K. et al. (2001). Absence of endothelial cells, central necrosis, and fibrosis are associated with aggressive inflammatory breast cancer. Cancer Research, 61(2), 445-51. Abstract below, free full text of article may be found at link above.
We recently established a new human inflammatory breast cancer (IBC) xenograft (WIBC-9) originating from a patient with IBC. The graft was transplantable in BALB/c nude and severe combined immunodeficient (SCID) mice. WIBC-9 was frequently accompanied by lung metastasis and exhibited erythema of the overlying skin, reflecting its human counterpart. Histological study of the original tumor and WIBC-9 revealed invasive ductal carcinoma with a hypervascular structure of solid nests and marked lymphatic permeation in the overlying dermis. In the central part of the solid nests, absence of endothelial cells, central necrosis, and fibrosis were observed. In vitro, WIBC-9 formed tube-like structures and loops, reflecting its in vivo feature and its human counterpart. WIBC-9 exhibited aneuploidy, ErbB-2 gene amplification, and an absence of estrogen receptor and progesterone receptor, which is consistent with IBC. Comparative studies of WIBC-9, three established non-IBC xenografts, and a human breast cancer cell line (SK-BR3) by reverse transcription-PCR, ELISA, and immunohistochemistry indicated that certain human genes (interleukin 8, vascular epidermal growth factor, basic fibroblast growth factor, angiopoietin 13, Flt-1, Tie-2, and Tie-1) and certain murine genes (integrin alpha(v)beta3, flt-1, tie-2, vascular epidermal growth factor, and CD31) were overexpressed in exposure to tumor cells. The molecular basis and these unique histological features may be associated with aggressive IBC on angiogenic and nonangiogenic pathways.
Kleer, CG. et al. (2001). Persistent E-cadherin expression in inflammatory breast cancer. Modern Pathology, 14(5), 458-64. Abstract below, free full text of article may be found at link above.
E-cadherin is a transmembrane glycoprotein that mediates epithelial cell-to-cell adhesion. Because loss of E-cadherin expression results in disruption of cellular clusters, it has been postulated that E-cadherin functions as a tumor suppressor protein. The role of E-cadherin in inflammatory breast cancer (IBC), a distinct and highly aggressive form of breast cancer, is largely unknown. The aim of our study was to elucidate whether E-cadherin expression contributes to the development and progression of the IBC phenotype and to investigate any differences in E-cadherin expression between IBC and stage-matched non-IBC. Forty-two breast cancer cases (20 IBC and 22 non-IBC) were identified. Strict and well-accepted criteria were used for the diagnosis of IBC. Clinical and pathologic features were studied, and formalin-fixed, paraffin-embedded tissue sections were immunostained for E-cadherin, estrogen and progesterone receptors (ER and PR, respectively), and HER2/neu. Statistical analysis was performed using Fisher’s exact test. All IBC uniformly expressed E-cadherin, whereas 15 of the 22 (68%) of the non-IBC expressed the protein (P = .006). Intralymphatic tumor emboli in the IBC cases were also all E-cadherin positive. Two IBC tumors demonstrated invasive lobular histology, and both cases were positive for E-cadherin. Of the non-IBC cases, three were invasive lobular carcinomas, and all were positive for E-cadherin. No association was found between E-cadherin expression and ER, PR status, or HER2/neu overexpression. Our study demonstrates that there is a strong association between E-cadherin expression and IBC and suggests that E-cadherin may be involved in the pathogenesis of this form of advanced breast cancer. In our study, we demonstrate that circulating IBC tumor cells strongly express E-cadherin, thereby providing an important exception to the positive association between E-cadherin loss and poor prognosis in breast cancer.
Tomlinson, JS., Alpaugh, AL., & Barsky, SH. (2001). An intact overexpressed e-cadherin/alpha,beta-catenin axis characterizes the lymphovascular emboli of inflammatory breast carcinoma. Cancer Research, 61(13), 5231-41. Abstract below, free full text of article may be found at link above.
The step of intravasation (lymphovascular invasion), a rate-limiting step in metastasis, is greatly exaggerated in inflammatory breast carcinoma (IBC). Comparing MARY-X with common non-IBC cell lines/xenografts, we discovered an overexpressed and overfunctioning E-cadherin/alpha,beta-catenin axis. In MARY-X, the E-cadherin and catenins were part of a structurally and functionally intact adhesion axis involving the actin cytoskeleton. In vitro, MARY-X grew as round compact spheroids with a cell density 5-10-fold higher than that of other lines. The spheroids of MARY-X completely disadhered when placed in media containing absent Ca(2+) or anti-E-cadherin antibodies or when retrovirally transfected with a dominant-negative E-cadherin mutant (H-2K(d)-E-cad). Anti-E-cadherin antibodies injected i.v. immunolocalized to the pulmonary lymphovascular emboli of MARY-X and caused their dissolution. A total of 90% of human IBCs showed increased membrane E-cadherin/alpha,beta-catenin immunoreactivity. These findings indicate that it is the gain and not the loss of the E-cadherin axis that contributes to the IBC phenotype.
Bertheau, P. et al. (2001). Allelic loss detection in inflammatory breast cancer: improvement with laser microdissection. Laboratory Investigation, 81(10), 1397-402. Abstract below, full text not available.
Solid tumors are composed not only of tumor cells but also of stromal nonneoplastic cells. In whole tumor samples, stromal cells retaining their alleles may therefore obscure detection of loss of heterozygosity (LOH) in tumor cells. An increasing number of studies have used laser-assisted tissue microdissection to improve LOH detection, but the real gain in sensitivity has been poorly quantified. We studied a group of 16 inflammatory breast carcinomas that were submitted to both standard DNA extraction from frozen whole tumor samples and laser microdissection performed on paraffin-embedded tumor samples. Using PCR with fluorescence-labeled primers, we comparatively analyzed ten polymorphic markers with both sources of DNA. With the LOH detection threshold set at -25%, we showed that 25 LOHs could not be diagnosed with whole tumor samples out of 73 LOHs positively diagnosed in microdissected samples (34%). With the LOH detection threshold set at -50%, the respective figures were 39 LOHs not diagnosed out of 55 LOHs (71%). Measuring the intensity of the allelic decrease, we showed that the mean decrease of the lost allele is -34% with whole tumor samples and -67% with microdissected samples. The increase in sensitivity of LOH detection with microdissection is associated with the density of stromal cells. This strong improvement in LOH detection in this aggressive type of breast cancer indicates that many other molecular studies performed on heterogeneous solid tumors may benefit from a first step of laser microdissection.”
Aziz, SA. et al. (2001). Case control study of prognostic markers and disease outcome in inflammatory carcinoma breast: a unique clinical experience. The Breast Journal, 7(6), 398-404. Abstract below, free full text not available.
Inflammatory breast carcinoma (IBC) is a rare but aggressive form of breast cancer. In this first-ever study, we investigated the role of nine prognostic markers’ expression (estrogen receptor [ER], progesterone receptor [PR], p53, C-erbB-2, epidermal growth factor receptor [EGFR], cathepsin D [CD], proliferating cell nuclear antigen [PCNA], DNA ploidy, and S-phase fraction [SPF]) and disease outcome in IBC cases compared with the control group. A case control study of IBC was conducted on 40 test cases with two controls per case matching age, grade, and number of axillary lymph nodes sampled. During 7 years of this study, 10% of all patients with breast cancer had IBC. In this study, 84% of IBC cases showed positive axillary lymph nodes compared with 63% in control group. The expression of nine prognostic markers, that is, ER, PR, p53, C-erbB-2, EGFR, CD, PCNA, SPF, and DNA ploidy, was studied by immunohistochemistry and flow cytometry. Hormone receptor status showed an inverse correlation (p < 0.05). Among p53, C-erbB-2, EGFR, and CD in the IBC group, only p53 showed a significant correlation, with 70% positivity in IBC versus 48% positivity in the control group (p < 0.05). Much higher SPF and PCNA positivity was seen in the IBC group compared with the control group (p < 0.05). DNA ploidy also showed a significant correlation compared with the control group (p < 0.05). After a median follow up of 18 months, median overall survival in the IBC group was 1.8 years (range 0.6-5.8 years) compared with 3.0 years (range 2.5-7.0 years), with a p value of 0.0001.
Kushwaha, AC. et al. (2000). Primary inflammatory carcinoma of the breast: retrospective review of mammographic findings. American Journal of Roentgenology, 174(2), 535-8. Abstract below, free full text at link above.
OBJECTIVE: Our goal was to describe the mammographic characteristics of primary inflammatory carcinoma of the breast. MATERIALS AND METHODS: We identified the medical records of 43 women who participated in a chemotherapy protocol for primary inflammatory carcinoma of the breast between 1994 and 1997. Mammograms were available for review in 26 women (age range, 34-78 years; mean age, 56 years). Two radiologists independently reviewed the 26 mammograms obtained before patients underwent treatment. A third observer was the final arbiter when needed. RESULTS: Mammographic findings included skin thickening in 24 patients (92%), diffusely increased density in 21 patients (81%), trabecular thickening in 16 patients (62%), axillary lymphadenopathy in 15 patients (58%), architectural distortion or focal asymmetric density in 13 patients (50%), and nipple retraction in 10 patients (38%). Malignant-appearing calcifications were seen in six patients (23%), and a mass was seen in four patients (15%). CONCLUSION: Diffuse mammographic abnormalities such as skin thickening, increased density, trabecular thickening, and axillary lymphadenopathy are common at presentation in patients with primary inflammatory carcinoma of the breast. Mammographic masses and malignant-appearing calcifications are uncommon manifestations of this disease.
Chin, PL., et al. (2000). Esthetic reconstruction after mastectomy for inflammatory breast cancer: is it worthwhile?. Journal of the American College of Surgeons, 190(3), 304-9. Abstract below, free full text not available.
BACKGROUND: Because inflammatory breast cancer (IBC) has been viewed as a malignancy with a poor likelihood of longterm survival, few women have been offered esthetic reconstruction after mastectomy for IBC. Recent advances in multimodality therapy have improved the outcomes for women with this disease. The purpose of this review was to assess the results of esthetic breast reconstruction in the population with IBC. STUDY DESIGN: Review of medical records at the City of Hope National Medical Center for the 10-year period ending in May 1997, revealed 23 women who underwent elective esthetic breast reconstruction after mastectomy for IBC. The records of these patients were reviewed retrospectively. Patients requiring reconstruction for large surgical chest wall defects were not included in the review. RESULTS: Treatment for IBC included mastectomy in all patients, chemotherapy in 22, and chest wall radiation therapy in 14. Immediate reconstruction was performed at the time of mastectomy (n = 14) or was delayed (n = 9). The types of reconstruction included transverse rectus abdominis musculocutaneous flap (n = 18), latissimus dorsi flap (n = 2), or prosthetic mammary implant reconstruction (n = 3). Seven women chose to undergo additional reconstruction procedures (ie, nipple reconstruction) after their initial reconstruction. With a median followup of 44 months for survivors, 16 patients developed recurrence after reconstruction. Of these, 6 were local recurrences and 10 were distant failures. Seven patients are currently alive with no evidence of disease, 4 are currently alive with disease, and 12 have died as a result of breast cancer. The median disease-free survival after reconstruction was 19 months. The median overall survival after reconstruction for all patients was 22 months. The only negative predictor of survival was a positive surgical margin at mastectomy. CONCLUSIONS: The significant emotional and esthetic benefits of breast reconstruction should be available to women with IBC. In light of the improving prognosis of IBC with current aggressive multimodality treatment, reconstructive procedures should be offered as part of comprehensive therapy.”
van Golen, KL., et al. (2000). RhoC GTPase, a novel transforming oncogene for human mammary epithelial cells that partially recapitulates the inflammatory breast cancer phenotype. Cancer Research, 60(20), 5832-8. Abstract below, free full text at link above.
Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer and is phenotypically distinct from other forms of locally advanced breast cancer. In a previous study, we identified specific genetic alterations of IBC that could account for a highly invasive phenotype. RhoC GTPase was overexpressed in 90% of IBC archival tumor samples, but not in stage-matched, non-IBC tumors. To study the role of RhoC GTPase in contributing to an IBC-like phenotype, we generated stable transfectants of human mammary epithelial cells overexpressing the RhoC gene. The HME-RhoC transfectants formed large colonies under anchorage-independent growth conditions, were more motile, and were invasive. In conjunction with an increase in motility, overexpression of RhoC led to an increase in actin stress fiber and focal adhesion contact formation. Furthermore, orthotopic injection into immunocompromised mice led to tumor formation. Taken together, these data indicate that RhoC GTPase is a transforming oncogene in human mammary epithelial cells and can lead to a highly invasive phenotype, akin to that seen in IBC.
Chang, S., et al. (2000). Inflammatory breast cancer survival: the role of obesity and menopausal status at diagnosis. Breast Cancer Research and Treatment, 64(2), 157-63. Abstract below, free full text not available.
No previous studies have evaluated the effect of body size and menopausal status at diagnosis on survival from inflammatory breast cancer (IBC). We evaluated whether obesity and menopausal status had an impact on IBC survival in a cohort of 177 female IBC patients seen from 1974 to 1993 at The University of Texas MD Anderson Cancer Center. Survival time was defined as time from diagnosis until death or censorship at last date of contact. We categorized women by body size by using the National Institutes of Health/National Heart, Lung, and Blood Institute’s definitions of obesity as body mass index ((BMI) = weight in kg/(height in m)2) > or = 30, overweight as 25 < or = BMI < 30kg/m2, and normal/lean as BMI < 25 kg/m2. Cox proportional hazards analysis, adjusting for axillary lymph node involvement and chemotherapy protocol, revealed a modifying effect of menopausal status at diagnosis on the association between obesity and IBC survival (P = 0.02). Relative to postmenopausal women, premenopausal women had significantly worse survival (hazard ratio (HR) = 1.51, 95% confidence interval (CI) = 1.03-2.22). After stratifying by menopausal status, premenopausal obese women had non-significantly better survival than their leaner premenopausal counterparts (HR = 0.63, 95% CI = 0.34-1.15) while postmenopausal obese women had significantly worse survival than their leaner counterparts (HR = 1.86, 95% CI = 1.02-3.40). These findings suggest that factors associated with larger body size at diagnosis may contribute to shorter IBC survival among postmenopausal women but not premenopausal women, who were found to have poorer survival regardless of body size.”
Amparo, RS., et al. (2000). Inflammatory breast carcinoma: pathological or clinical entity?. Breast Cancer Research and Treatment, 64(3), 269-73. Abstract below, free full text not available.
Inflammatory breast carcinoma (IBC) diagnosis is usually based in the presence of typical clinical symptoms (redness and edema in more than 2/3 of the breast), which are not always associated with pathologic characteristics (subdermal lymphatics involvement). Whether exclusively pathologic findings without clinical symptoms are sufficient for IBC diagnosis remains controversial. A retrospective analysis of 163 clinically diagnosed IBC (CIC) either with dermal lymphatics invasion or not, was compared with another group of 99 patients with dermal lymphatics invasion without clinical symptoms (occult inflammatory carcinoma) (OIC). The following clinical and pathological characteristics have been analyzed and compared: age, menopausal status, clinical axillar node involvement, symptoms duration before diagnosis, grade, estrogen receptors, presence of metastases at diagnosis, local recurrence, metastasic dissemination, disease-free (DFS) and overall survival (OS). Median age was younger in CIC (52.3 vs. 63.8 years; p < 0.001). Symptom duration before diagnosis were significantly shorter in CIC (3.4 vs. 6.8 months: p < 0.0001). Visceral (36.2% vs. 17.2%; p = 0.001) and brain metastases (7.4% vs. 1%; p = 0.02) was significantly more frequent in CIC. Negative estrogen receptors were more frequent in CIC (34.9% vs. 65.1%: p < 0.004). Five-years DFS (25.6 vs. 51.6%; p < 0.0001) and OS (28.6 vs. 40%; p < 0.05) were shorter in CIC. CIC (regardless of subdermal lymphatics involvement) must be clearly differentiated from OIC. Prognosis of CIC patients is poorer, so this two entities should be clearly differentiated when therepeutic results are reported.”
Kleer, CG., van Golen, KL., & Meravjer, SD. (2000). Molecular biology of breast cancer metastasis. inflammatory breast cancer: clinical syndrome and molecular determinants. Breast Cancer Research, 2(6), 423-9. Abstract below, free full text at link above.
Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer (LABC) that effects approximately 5% of women with breast cancer annually in the USA. It is a clinically and pathologically distinct form of LABC that is particularly fast growing, invasive, and angiogenic. Nearly all women have lymph node involvement at the time of diagnosis, and approximately 36% have gross distant metastases. Despite recent advances in multimodality treatments, the prognosis of patients with IBC is poor, with a median disease-free survival of less than 2.5 years. Recent work on the genetic determinants that underlie the IBC phenotype has led to the identification of genes that are involved in the development and progression of this disease. This work has been aided by the establishment of primary human cell lines and animal models. These advances suggest novel targets for future interventions in the diagnosis and treatment of IBC.