Inflammatory breast cancer defined: proposed common diagnostic criteria to guide treatment and research.

PURPOSE: Inflammatory breast cancer is a deadly and aggressive type of breast cancer. A key challenge relates to the need for a more detailed, formal, objective definition of IBC, the lack of which compromises clinical care, hampers the conduct of clinical trials, and hinders the search for IBC-specific biomarkers and treatments because of the heterogeneity of patients considered to have IBC. METHODS: Susan G. Komen, the Inflammatory Breast Cancer Research Foundation, and the Milburn Foundation convened patient advocates, clinicians, and researchers to review the state of IBC and to propose initiatives to advance the field. After literature review of the defining clinical, pathologic, and imaging characteristics of IBC, the experts developed a novel quantitative scoring system for diagnosis. RESULTS: The experts identified through consensus several "defining characteristics" of IBC, including factors related to timing of onset and specific symptoms. These reflect common pathophysiologic changes, sometimes detectable on biopsy in the form of dermal lymphovascular tumor emboli and often reflected in imaging findings. Based on the importance and extent of these characteristics, the experts developed a scoring scale that yields a continuous score from 0 to 48 and proposed cut-points for categorization that can be tested in subsequent validation studies. CONCLUSION: To move beyond subjective 'clinical diagnosis' of IBC, we propose a quantitative scoring system to define IBC, based on clinical, pathologic, and imaging features. This system is intended to predict outcome and biology, guide treatment decisions and inclusion in clinical trials, and increase diagnostic accuracy to aid basic research; future validation studies are necessary to evaluate its performance.

Chemotherapeutic palliative approaches in the treatment of breast cancer.

The palliative approach to the treatment of metastatic breast cancer deserves discussion because of the numerous patients diagnosed with this disease. Approximately 10% of the greater than 180,000 women diagnosed with breast cancer each year will present with metastatic disease, and an additional 50% to 70% will eventually relapse. The clinician must consider the treatment toxicity, efficacy, and impact on quality of life to arrive at the optimal therapeutic decision. The following discussion will provide an overview of palliative treatment options, including single-agent and combination chemotherapy, as well as new alternative drugs, such as paclitaxel and vinorelbine. Treatment toxicity and its impact on quality of life will be emphasized.

Ifosfamide in the treatment of breast cancer.

Ifosfamide is an alkylating agent that has demonstrated efficacy in the treatment of several malignancies. Preclinical data also support non-cross-reactivity between cyclophosphamide and ifosfamide in several cell lines. These data suggest that ifosfamide may be highly effective in the salvage setting for breast cancer patients who have received previous treatment with cyclophosphamide. Unfortunately, the available data on ifosfamide use in advanced disease are derived from poorly designed studies that evaluated various patient populations and dosing schedules. This review examines the efficacy of ifosfamide in salvage therapy for breast cancer and emphasizes the need to determine the optimal dosing schedule for ifosfamide used as a single agent or in combination chemotherapy for advanced breast cancer.

High-dose chemotherapy with autologous peripheral blood progenitor cell support for primary breast cancer in patients with 4-9 involved axillary lymph nodes.

Breast cancer patients with more than three involved axillary lymph have a high likelihood of relapse after adjuvant therapy. Early results of administration of high-dose chemotherapy (HDCT) and autologous peripheral blood progenitor cells (PBPC) to patients with primary breast cancer and > or = 10 involved axillary nodes have been encouraging. We performed a multicenter trial to determine whether HDCT could be safely administered to patients with primary breast cancer involving 4-9 axillary lymph nodes. Fifty-four patients with stage II or III breast cancer and 4-9 involved axillary lymph nodes received doxorubicin-based induction chemotherapy, followed by high-dose cyclophosphamide (5.625 g/m2), cisplatin (165 mg/m2), and BCNU (450 mg/m2) and PBPC mobilized by sargramostim (GM-CSF) or filgrastim (G-CSF). After completion of HDCT, patients received radiation therapy to the chest wall or involved breast, plus tamoxifen. Survival and disease-free survival, time to engraftment, and charges associated with HDCT were determined. Plasma concentrations of BCNU were determined and plasma AUC(BCNU) was calculated. Fifty-four patients were evaluable for survival and relapse-free survival. Fifty-two patients received HDCT with PBPC support and were evaluable for toxicity. Fifteen patients (29%) developed late pulmonary drug toxicity, which resolved with a 10-week course of corticosteroids in all but one affected patient, who subsequently died of pulmonary toxicity. Ten patients relapsed a median of 426 days (range 86-1117 days) after the start of induction chemotherapy, seven of whom have died. Forty-three patients are alive and breast cancer-free at a median of 947 days (range 661-1730 days) after the start of therapy, including one patient who developed myelodysplastic syndrome 809 days after the start of HDCT. Actuarial 4-year survival and disease-free survival from the start of treatment are 84 and 71%, respectively. Mean plasma AUC(BCNU) was 400 (range 82-1255) microgxmin/ml and was not statistically different from that measured in historical controls who received 600 mg/m2 of BCNU. Combined hospital and physician charges for patients treated at the University of Colorado decreased from a mean of $125845 for the first four patients to $77126 for the final seven patients. We conclude that HDCT with autologous PBPC can be administered with acceptable safety to patients with primary breast cancer involving 4-9 axillary lymph nodes. An ongoing, prospective randomized trial is evaluating the efficacy of HDCT for this patient group.

High-dose chemotherapy with autologous stem cell support for breast cancer.

Breast cancer is a major public health issue, expected to affect one out of nine women over a lifetime. High-dose chemotherapy with autologous stem cell support is a current approach to the management of metastatic breast cancer and high-risk primary breast cancer. This review considers the effectiveness of this modality in the treatment of breast cancer in an effort to define its role in overall patient management. Current research directions, including technical advances aimed at reducing toxicity, are discussed. Finally, controversies regarding the role of third-party payers in the investigational process are considered.

Uniformity of liver density and nonheme (storage) iron distribution.

The extent of variation in tissue density and hepatic nonheme iron concentration has been examined at autopsy in 21 adult livers. Samples were taken from each liver at inferior and superior sites in the midaxillary, anterior axillary, and midclavicular lines. Histologic examination showed diffuse metastatic carcinoma, cirrhosis, fibrosis, necrosis, steatosis, or congestion in 19 livers; two livers were normal. Density was determined by saline displacement of 0.5- to 1.0-g specimens. Nonheme iron concentration was measured at each site in samples of the size obtained by wedge (0.5 to 1.0 g) and percutaneous needle (0.005 to 0.010 g) biopsy using specially developed chemical assays. Density was uniform within each liver. Despite the inclusion of diseased tissues, the variation in density among the 21 livers was small (coefficient of variation, 1.25%). The mean (+/- 1 SD) hepatic density was 1.051 +/- 0.013 g/mL (range, 1.017 to 1.077 g/mL). Within each liver, the nonheme iron also was uniformly distributed among the six sites. Chemical measurements of nonheme iron concentration were not significantly different in samples of the size obtained by wedge or percutaneous liver biopsy. All the hepatic nonheme iron determinations were below the upper 95% confidence limit of concentrations in adult males (480 micrograms/g). In the absence of focal lesions, the uniformity in hepatic density and nonheme iron distribution supports the assumption of several clinical methods for measuring liver storage iron (wedge and needle biopsy, determination of hepatic magnetic susceptibility, computed tomography, and magnetic resonance imaging) that one sample of liver tissue is representative of the whole organ.

The breast cancer prevention trial (P-1 study). The role of tamoxifen in preventing breast cancer.

The recently completed Breast Cancer Prevention Trial found that tamoxifen can reduce the incidence of breast cancer by nearly half in women at high risk, but the benefit comes at a price of increased risk of endometrial cancer and thromboembolism. This article reviews the actions of tamoxifen and the design, findings, and implications of this study.

Chemotherapy in the management of breast cancer.

BACKGROUND: Breast cancer has become a national health problem, affecting more than 180,000 women each year. Although advances in early detection and treatment have been made, it remains the second leading cause of cancer-related death in women. KEY POINTS: The treatment of breast cancer requires the careful integration of systemic and local methods. Although the application of hormonal therapy or chemotherapy is becoming less distinct, this discussion will review the important clinical trials and future directions of chemotherapy in the management of breast cancer. Data support the use of chemotherapy in the adjuvant setting, for preoperative tumor reduction of locally advanced disease, and as palliation in metastatic disease. The optimal chemotherapeutic regimen is not known; however, data support a role for adjuvant doxorubicin in node-positive disease, neoadjuvant therapy for high-risk disease, and high-dose chemotherapy to consolidate responding metastatic disease. CONCLUSIONS: The clinician must determine the risks and potential benefits of systemic chemotherapy before recommending treatment strategies. Although progress has been made, future advances can only occur through active participation in clinical trials.