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2000: A case of inflammatory breast cancer following augmentation mammoplasty with silicone gel implants.
Breast Cancer 2000 Jan;7(1):71-4, Kasamaki S, et al.
“A 54-year-old-woman who underwent augmentation mammoplasty with silicone gel implants 30 years previously, visited our hospital with complaints of bloody nipple discharge, redness and itching of her right breast. Cancer of the right breast was diagnosed by dynamic magnetic resonance imaging (MRI) examination with Gadolinium (Gd)-DTPA enhancement. Radical mastectomy was subsequently performed. The histopathological findings demonstrated scirrhous and inflammatory breast cancer with invasion of dermal lymphatics. ”
2000: Primary inflammatory carcinoma of the breast: retrospective review of mammographic findings.
AJR Am J Roentgenol 2000 Feb;174(2):535-8, Kushwaha AC, et al.
“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.
2000: The Role of the RhoC GTPase Oncogene in Inflammatory Breast Cancer.
AACR Poster 4533, van Golen, KL, et al.
“Inflammatory breast cancer (IBC) is an extremely aggressive and metastatic form of breast cancer that has a 5-year disease-free survival rate of less than 45%. Little is known about the genetic components of the disease. We identified 17 genes by differential display comparing the SUM149 IBC cell line with two normal human mammary epithelial (HME) cell lines, and the patients own lymphocytes. Twenty-nine IBC and 19 stage-matched non-inflammatory breast tumors from patients were probed for expression of these genes by in situ hybridization. Two genes were found to be concordantly altered in 91% of IBC versus 0% of the non-inflammatory samples analyzed. RhoC GTPase, a putative oncogene, was found to be over-expressed, while expression of a novel gene, LIBC, was found to be lost in most of the IBC samples analyzed. To understand what role these genes play in the metastatic IBC phenotype, stable transfectants of HME cells over-expressing RhoC were established. The transfectants were found to form 10-100-fold more colonies in soft agar than control-transfected HME cells. And, in a Matrigel invasion assay had, on average, a 5-fold increase in invasion over the control cells. When evaluated for production of angiogenic factors, the RhoC transfectants produced VEGF to ~90% the level of the SUM149 IBC cell line. Preliminary in vivo data indicates that the HME RhoC transfectants are able to form tumors in nude mice. Taken together these data support that RhoC acts as an oncogene in IBC and likely is a key determinant of it s metastatic phenotype.”
2000: Esthetic reconstruction after mastectomy for inflammatory breast cancer: is it worthwhile?“
J Am Coll Surg 2000 Mar;190(3):304-9, Chin PL, et al.
“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.”
2000: Multimodality therapy in inflammatory breast cancer: is there a place for surgery?
Ann Oncol 2000 Sep;11(9):1147-53, De Boer, RH, et al.
“BACKGROUND: In many centres surgery is used as part of a combined modality approach to the treatment of inflammatory breast cancer (IBC). Nevertheless, its value is controversial given the high risk of metastatic relapse and poor overall prognosis. We have reviewed patients with true IBC prospectively treated at the Royal Marsden Hospital in chemotherapy trials to assess further the role of surgery as part of combined modality treatment. PATIENTS AND METHODS: Fifty-four patients who had responsive or stable disease to primary chemotherapy went on to have either radiotherapy alone (n = 35) or surgery plus radiotherapy (n = 19); the decision on surgery was based partly on clinician preference and partly on clinical response. RESULTS: The 35 patients undergoing radiotherapy alone had a median progression-free survival (PFS) of 16 months and median overall survival (OS) of 35 months. Twenty-four patients (69%) have relapsed with a total of twelve (34%) relapsing locally. In comparison, the 19 patients receiving both surgery and radiotherapy had a PFS of 20 months, and a median OS of 35 months. Fifteen patients (79%) have relapsed, eight (42%) of these locally. None of these differences were statistically significant. CONCLUSIONS: These results do not suggest a clinical advantage for surgery in addition to chemotherapy and radiotherapy for patients with IBC. They support the need for a prospective randomised trial to address this question.”
2000: RhoC GTPase overexpression modulates induction of angiogenic factors in breast cells.
Neoplasia 2000 Sep-Oct;2(5):418-25, van Golen, KL, et al.
“Inflammatory breast cancer (IBC) is a distinct and aggressive form of locally advanced breast cancer. IBC is highly angiogenic, invasive, and metastatic at its inception. Previously, we identified specific genetic alterations of IBC that contribute to this highly invasive phenotype. RhoC GTPase was overexpressed in 90% of archival IBC 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, and studied the effect of RhoC GTPase overexpression on the modulation of angiogenesis in IBC. Levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin-6 (IL-6), and interleukin-8 (IL-8) were significantly higher in the conditioned media of the HME-RhoC transfectants than in the untransfected HME and HME-beta-galactosidase control media, similar to the SUM149 IBC cell line. Inhibition of RhoC function by introduction of C3 exotransferase decreased production of angiogenic factors by the HME-RhoC transfectants and the SUM149 IBC cell line, but did not affect the control cells. These data support the conclusion that overexpression of RhoC GTPase is specifically and directly implicated in the control of the production of angiogenic factors by IBC cells.”
2000: RhoC GTPase, a novel transforming oncogene for human mammary epithelial cells that partially recapitulates the inflammatory breast cancer phenotype.
Cancer Res 2000 Oct 15;60(20):5832-8, van Golen, KL, et al.
“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.”
2000: Inflammatory breast cancer survival: the role of obesity and menopausal status at diagnosis.
Breast Cancer Res Treat 2000 Nov;64(2):157-63, Chang, S, et al.
“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.”
2000: Inflammatory breast carcinoma: pathological or clinical entity?
Breast Cancer Res Treat 2000 Dec;64(3):269-73, Amparo RS, et al.
“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.”
2000: Molecular biology of breast cancer metastasis. Inflammatory breast cancer: clinical syndrome and molecular determinants.
Breast Cancer Res 2000;2(6):423-9, Kleer, CG, et al.
“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.“
