Higher incidence of aggressive breast cancers in African-American women: a review.

Despite a lower incidence of breast cancers in African Americans than in Caucasians, mortality rates from breast cancer are higher in African Americans. This review summarizes disparate characteristics of breast cancer diagnosed in African Americans as compared with Caucasians, such as more advanced stage at diagnosis and less estrogen-receptor positivity of disease, in an effort to explain differences in their survival outcomes. Multifactorial explanations are offered, including differences in access to care, disparate utilization of mammography screening and often differences in treatment course-as well as biologic factors, such as higher incidence of aggressive breast cancer phenotypes, higher grade of tumor and higher growth index of tumors in African Americans as compared with Caucasians. Multiple population-based studies have been reviewed and screening and treatment interventions proposed in order to heighten awareness of these differences and to improve disease outcomes among this high-risk population.

Bisphosphonate therapy for women with breast cancer and at high risk for osteoporosis.

Bisphosphonates are effective inhibitors of osteoclast activity and bone resorption, and are standard treatments for osteoporosis, hypercalcemia of malignancy, and metabolic bone disease. Bisphosphonates have also been established to effectively reduce skeletal-related events due to malignancy metastatic to bone. Bisphosphonates are now being incorporated into breast cancer treatment regimens in order to combat osteoporosis caused by ovarian suppression, chemotherapy treatment, aromatase inhibitors and the postmenopausal state itself. A large body of evidence suggests that African-American women are at higher risk for osteoporosis-related morbidity than their Caucasian counterparts. In this review, we highlight recommendations toward screening for osteoporosis in high-risk populations. We summarize the mechanisms of action of bisphosphonates in the treatment of osteoporosis and then summarize national recommendations toward incorporating the use of bisphosphonates as support for the bone health of breast cancer patients, as well as patients at high risk for osteoporosis.

Chemoprevention of breast cancer for women at high risk.

Breast cancer remains the second most common cause of cancer death in the United States. Several studies have identified cohorts of women at higher than average risk to develop this disease. These are women who are exposed to high levels of endogenous or exogenous estrogens, those with a family history of breast cancer, and those who harbor benign breast disease or genetic mutations that predispose to breast cancer. In this population group, adapting a chemoprevention strategy to decrease the risk of developing overt disease is a strong consideration. To this end, tamoxifen is the most studied agent to date. This article describes high-risk categories that predict future development of invasive breast cancer, summarizes the currently available data to support the use of tamoxifen for chemoprevention, and discusses the adverse effects of tamoxifen, as well as measures to anticipate and monitor for possible adverse outcomes.

Toxicity of aromatase inhibitors.

Adjuvant hormonal therapy in hormone receptor-positive breast cancer is used for the prevention of disease recurrence and prolongation of survival. Aromatase inhibitors are increasingly being used for this purpose. Numerous studies now reveal their benefits over tamoxifen while demonstrating a markedly different toxicity profile. With greater use, a better understanding of the long-term effects of aromatase inhibitors on the prevention of cancer recurrence and on their long-term effects on chronic comorbid conditions will develop. Recognizing and understanding these toxicities, as well as the differences among the various aromatase inhibitors, will be crucial for all clinicians. When choosing the type of adjuvant hormonal therapy for each individual patient, comorbidities and quality-of-life parameters must be considered. In addition, ongoing studies evaluating these agents directly should reveal differences among them that may aid in determining the principal agent for use in this setting. In this article, we review the known toxicity profile of aromatase inhibitors and the current guidelines that exist in the diagnoses and management of these toxicities.

Phase II study of fludarabine and alpha-interferon in patients with low-grade non-Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES: Low-grade non-Hodgkin's lymphoma (NHL) remains incurable with standard dose chemotherapy. Nucleoside analogs such as fludarabine are effective, but even when used as initial therapy, the median duration of remission ranges from only 16 to 24 months. Interferon (IFN) is also active and has been investigated both by incorporating it into the chemotherapy regimen and/or as maintenance therapy, where it may prolong remission. We designed a phase II trial of alternating fludarabine and IFNalpha2a to determine response rate, time to progression and toxicity of this regimen in patients with advanced stage low-grade NHL or mantle cell lymphoma. DESIGN AND METHODS: Patients had received 0-2 prior regimens that did not include nucleoside analogs or IFN and had adequate organ function. Fludarabine was administered intravenously at 25 mg/m2/day for 5 days once every 6 weeks with IFN in weeks 4 and 5 at 3x10(6) U/m2 subcutaneously three times weekly for 6 doses. Treatment continued in responders for 2 cycles past maximal response (minimum 6 cycles). No maintenance was given. RESULTS: Between 1994 and 1999, 31 patients were accrued and were evaluable for toxicity, with 29 eligible for evaluation of response. Toxicity was primarily myelosuppression, with grade 3 neutropenia in 12 patients and grade 4 thrombocytopenia in one patient. The overall response rate was 51.7% (15/29), including 6 complete and 9 partial responses. With a median follow-up of 35.6 months, the median overall survival was 60.8 months, and the median time to disease progression (TTP) was 12.6 months. Of the 15 responding patients, treatment-naive patients had a median response duration of 39.6 months with a median TTP of 42.1 months, while the median response duration was 5.2 months with a median TTP of 14.5 months in patients who had received prior treatment (p=0.0065 and 0.0374, respectively). INTERPRETATION AND CONCLUSIONS: This schedule of alternating fludarabine with IFN does not seem to increase response rate appreciably, but there are some prolonged responses, particularly in previously untreated patients. Given the non-overlapping toxicities of IFN with those of chemotherapy and antibody-based therapeutics, there may be a role for combination therapies, especially if the biological basis of response to IFN can be elucidated.