Aman U. Buzdar, MD

In metastatic breast cancer (MBC), lapatinib (Tykerb) + letrozole (Femara) delayed disease progression in HER2+, HR+ patients, according to initial results from a phase III trial (EGF30008) presented by Stephen Johnston, MD (abstract 46).

Based on 2 meta-analyses of nearly 20,000 HR+ early breast cancer patients, AIs are superior to tamoxifen in reducing recurrences, whether as initial monotherapy or given in a “switching” strategy (abstract 12).

Eidtmann H et al: The effect of zoledronic acid on aromatase inhibitor associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36 months follow-up of ZO-FAST (abstract 44).

There is evidence that higher doses of fulvestrant (Faslodex) may have greater activity than the approved dose of 250 mg/mo. The FIRST trial (Fulvestrant First-Line Study) compared 500 mg vs anastrozole 1 mg/d in the first-line advanced disease setting, finding that a dose of 500 mg/mo achieved response rates and clinical benefit rates similar to those obtained with anastrozole 1 mg/d but gave a significantly longer time to progression (abstract 6126).

EXPERT’S CORNER-Nearly three quarters of breast cancer patients have tumors that express estrogen receptors (ERs) or progesterone receptors (PRs); approximately half of these patients are postmenopausal. We look to endocrine therapy, therefore, to prevent recurrences and save lives in the majority of early breast cancer patients and to prolong survival in the advanced disease setting.

ABCSG Trial: Survival Benefit for Tamoxifen. Anastrozole Updated results from Austrian Breast and Colorectal Cancer Study Group Trial 8 confirmed a survival difference for the sequencing strategy of tamoxifen followed by anastrozole (Arimidex), compared to 5 years of tamoxifen (abstract 14). Preliminary results (median follow-up 55 mo) had previously revealed a 24% reduction in recurrence in favor of the sequencing strategy, although the difference was not statistically significant.

One of the best examples of the "bench to bedside" process is the development of trastuzumab (Herceptin) for HER2-overexpressed breast tumors. From the identification of the neu oncogene in 1984[1] and its subsequent cloning,[2] to the development of a humanized monoclonal antibody targeting HER2 that improved outcome not only in the metastatic setting[3] but also in the adjuvant setting[4-7] has been a long yet fruitful journey.

Over the past 20 years we have witnessed the emergence of a new generation of aromatase inhibitors as valuable antiestrogens in the management of both advanced and early-stage breast cancer. In addition, the list of cytotoxic chemotherapeutic agents useful in the control of breast cancer has grown considerably. The emergence of anthracyclines was a major chemotherapeutic step forward in the 1980s, and the taxanes have clearly been the agents with the greatest impact on breast cancer treatment over the past decade. The end of the past 2 decades has been characterized by a greater understanding of the molecular biology of breast cancer, rational drug design, and the development of agents that disrupt specific cellular targets and pathways. The development of better prognostic and predictive assays that employ a panel of genes involved in the malignant and metastatic phenotype promises to allow clinicians to better select patients who could forgo adjuvant chemotherapy. Finally, adjunctive and supportive therapy of breast cancer has evolved substantially over the past 20 years. This review will highlight some of the landmark accomplishments during this time, and offer a glimpse at where we might be 20 years from now.

This review of adjuvant chemotherapyby Perez and Muss isconcise and complete. For themost part, the authors present the datain a balanced way. The role of adjuvantchemotherapy has been establishedin breast cancer. Appropriateutilization of adjuvant chemotherapycan significantly reduce the risk ofdisease recurrence and improve survival.These benefits are associatedwith adjuvant chemotherapy regardlessof the age of the patient, nodalstatus, or hormonal status of cancer.

Drs. Patridge and Schapira setout to review breast cancerand pregnancy, discuss treatmentoptions for breast cancer duringpregnancy, and summarize the availableevidence regarding safety of pregnancyafter breast cancer. This is asubstantial undertaking. They beginby reviewing the epidemiologic dataindicating an early increase in risk ofbreast cancer development after pregnancyand the likely long-term protectiveeffect of pregnancy on breastcancer risks. The subsequent focus oftheir review is on breast cancer duringpregnancy, a relatively rare occurrence.In a study from California,Smith et al indicated that the frequencyof breast cancer concurrent withpregnancy was 1.3 per 10,000 livesingleton births.[1] The authors notea frequently quoted figure of 1 in 3,000pregnancies.

Carcinoma of the breast is the most common cancer in women in the United States and is second only to lung cancer as a cause of cancer death in women. The incidence of breast cancer has risen steadily over the past decade, with the most dramatic increase seen in smaller primary breast tumors, partly because widespread use of screening mammography permits earlier detection [1].

Most men with breast cancer present with a mass in the breast, theevaluation of which should include a tissue diagnosis. If the presence ofinvasive cancer is established, adequate local therapy includes totalremoval of the breast. Most tumors are hormone-receptor positive. Inhigh-risk patients, the use of endocrine adjuvant therapy and/or combinedendocrine and chemotherapy should be considered. Patients withestrogen-receptor (ER)-negative disease should be offered chemotherapy.In patients with metastatic disease and ER-positive tumors, initialtreatment should be endocrine therapy; systemic chemotherapy shouldbe used in patients who are either hormone-receptor negative or resistantto available endocrine therapies.

Anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin) are members of the third generation of aromatase inhibitors that has now replaced aminoglutethimide (Cytadren), the progestins, and tamoxifen

Adjuvant chemotherapy represents a significant advance in the management of early-stage breast cancer and, as such, has saved many lives. Worldwide, adjuvant chemotherapy has benefitted all groups tested, including

Endocrine therapy is the oldest form of treatment for metastatic breast cancer. The availability of numerous new endocrine agents during the past 10 years has led to significant changes in the use of this form of therapy. This article identifies

Endocrine therapy has long been a mainstay in the therapy of metastatic breast cancer and in the adjuvant setting. The introduction of anastrozole (Arimidex) to the market in 1996 has provided another option for such treatment. Drs. Goss and Tye provide a thorough review of anastrozole and outline its advantages over other aromatase inhibitors as adjuvant therapy for breast cancer and its potential use in the treatment of early breast cancer. The authors delineate many important issues regarding the use of anastrozole; an understanding of these issues is imperative for the optimal utilization of this therapy. The paper has two shortcomings: (1) It focuses almost solely on aromatase inhibitors, to the neglect of other endocrine therapies. (2) Many references are unconventional and represent data on file with various drug manufacturers, which are not easily accessible to readers.