Breast Cancer

The use of aromatase inhibitorshas increased dramatically inthe past few years as a resultof the emergence of new, more specificagents, such as anastrozole(Arimidex), exemestane (Aromasin),and letrozole (Femara). This class ofagents effectively blocks the peripheralformation of estradiol, decreasingits concentration to less than 10%,while maintaining selectivity.[1]Evaluation of these selective aromataseinhibitors as adjuvant therapyfor early-stage breast cancer wasbased on the findings of trials inmetastatic breast cancer, summarizedby Visvanathan and Davidson, thatdemonstrated the equivalence and,in some cases, superiority of thearomatase inhibitors comparedwith megestrol and tamoxifen,including their superior side-effectprofile.[2-4]

Breast cancer oncologists makechoices between agents withinthe same therapeutic classevery day-eg, paclitaxel vs docetaxel(Taxotere), doxorubicin vs epirubicin(Ellence), tamoxifen vs anaromatase inhibitor. In the case ofchemotherapeutic agents, we do notyet have results from adequately powereddirect comparisons, and so, decisionsare based on indirectcomparisons between trials, safetyconsiderations, side-effect profiles,cost considerations, and clinical experience.In the case of adjuvantaromatase inhibitor therapy vs tamoxifen,the results of a huge trial areavailable to consider and, indeed, reconsider.In the years to come, theArimidex, Tamoxifen Alone or inCombination (ATAC) trial experiencewill be augmented with resultsfrom multiple other trials that addressalmost all the worthwhile clinicalquestions (except 5 vs 10 yearsof an aromatase inhibitor).

BEIRUT, Lebanon-Vinorelbine (Navelbine) plus capecitabine (Xeloda) is a highly effective and well tolerated first-line chemotherapy regimen for metastatic breast cancer, according to results of a recent 30-patient multicenter phase II trial. Investigators reported a response rate of 67%, with the main toxicity being grade 3/4 neutropenia in 13% of patients.

The aromatase inhibitors are regarded as standard approaches tofirst- or second-line endocrine therapy in women with hormoneresponsivemetastatic breast cancer. Their efficacy and apparent lackof toxicity have led to their evaluation as adjuvant therapy. Althoughinitial results with these agents in early breast cancer are promising,our collective long-term experience documenting tamoxifen’s benefitsand our uncertainty about the long-term effects of aromatase inhibitorssuggest that it is too early to recommend their routine use in theadjuvant setting. However, anastrozole is also a reasonable therapeuticoption in the adjuvant setting, particularly in individuals with acontraindication to tamoxifen such as those with thromboembolicdisease or those who develop breast cancer while receiving tamoxifenor raloxifene (Evista) therapy. Anastrozole (Arimidex) was recentlyapproved by the Food and Drug Administration for the adjuvanttreatment of postmenopausal women with hormone-receptor–positiveearly breast cancer. Ongoing trials are assessing the potential role ofaromatase inhibitors in the adjuvant, neoadjuvant, and preventivesettings.

SAN ANTONIO-In the first phase II trial of gefitinib (Iressa, also known as ZD1839) in breast cancer, the agent showed limited activity in patients with heavily pretreated metastatic breast cancer, according to a report presented at the 25th Annual San Antonio Breast Cancer Symposium (abstract 20).

SAN ANTONIO-A condensed, 14-day schedule of doxorubicin (Adria-mycin), cyclophosphamide, and pacli-taxel (Taxol) proved superior to conventional scheduling of the three drugs in a Cancer and Leukemia Group B (CALGB) trial reported at the 25th Annual San Antonio Breast Cancer Symposium (abstract 15). According to study investigator Marc L. Citron, MD, the dose-dense scheduling resulted in significant improvements in both disease-free and overall survival-and, with filgrastim (Neupogen) support, did not increase drug toxicity.

ORLANDO-A computer-based diagnostic system for breast cancer using magnetic resonance spectroscopy (MRS) plus a statistical classification strategy (SCS) is ready for acceptance testing in the clinic, Australian researchers said at the Era of Hope Department of Defense Breast Cancer Research meeting.

SEATTLE-A Fred Hutchinson Cancer Research Center study documents important disparities in breast cancer diagnosis, treatment, and survival among American women of various ethnicities. The findings by Christopher Li, MD, PhD, and his colleagues (Arch Intern Med 163:49-56, 2003) are based on data from 11 tumor registries participating in the Surveillance, Epidemiology, and End Results (SEER) program, including 124,934 women diagnosed with first primary invasive breast cancer from 1992 to 1998.

SAN ANTONIO-The three-drug combination of carboplatin (Paraplatin), paclitaxel (Taxol), and trastuzumab (Herceptin) increases response rate and time to progression among HER-2-positive patients with advanced breast cancer, compared with the trastuzumab/paclitaxel combination alone, according to Nicholas J. Robert, MD, chairman of research at Inova Fairfax Hospital’s Cancer Center, Fairfax, Virginia, and co-chairman of the Breast Committee of the US Oncology Research Network.

ORLANDO-Intratumoral injection of dendritic cells genetically modified to express CD40 ligand (CD40L) eradicated breast tumors in mice, Zoya R. Yurkovetsky, a PhD student from the Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, reported at the Era of Hope Department of Defense Breast Cancer Research Program meeting.

NEW ORLEANS-Eighteen-year results from a pivotal trial comparing lumpectomy with mastectomy have demonstrated maintenance of efficacy for the breast-sparing treatment. Matthew Poggi, MD, of the Radiation Oncology Branch of the National Cancer Institute, updated the study results at the American Society for Therapeutic Radiology and Oncology (abstract 91).

ORLANDO-Breast cancer patients who received targeted home nursing visits after a short-stay surgery used fewer postoperative health services and had improved social and family well-being, compared with patients receiving no visits or nontargeted visits. Gwen K. Wyatt, RN, PhD, associate professor of nursing, Michigan State University, presented the study results at the Era of Hope Department of Defense Breast Cancer Research Program meeting. The study included 240 female breast cancer patients. Short hospital stay was defined as 48 hours or less. Patients were 21 years of age or older and fluent in English. The majority were white, married, and employed prior to surgery.

ORLANDO-Women with a specific prohibitin fragment genotype (T allele) and a first-degree relative with breast cancer appear to be at greater risk of developing the disease than women with the prohibitin C allele genotype, reported Eldon R. Jupe, PhD, senior research scientist, Immunology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City.

NEW ORLEANS-Template-based interstitial brachytherapy is an effective method for treating breast cancer, according to a study presented at the 44th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (abstract 147). The study is one of the first to use a template to position interstitial implants in its entire study population as part of its protocol.

NEW ORLEANS-Toxicity for low-dose-rate and high-dose-rate accelerated partial breast irradiation (APBI) (brachytherapy) is comparable to that observed in women treated with conventional whole breast external beam radiation therapy after lumpectomy, according to a 10-year study (RTOG 95-17) presented at the 44th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (abstract 146).

Sharon Krumm, PhD, RN, the Editor of Oncology Nursing, is administrator and director of nursing, Johns Hopkins Oncology Center, and assistant professor, Johns Hopkins University Schools of Medicine and Nursing. ONI is pleased to announce the creation of an Editorial Advisory Board for Oncology Nursing. Members are Catherine Coleman, RN, OCN, a consultant for breast center development, Tiburon, California, and Mary McCabe, BSN, MA, acting director, Office of Communications, National Cancer Institute, Be-thesda, Maryland. See p. 27 for more about the board members.

ORLANDO-A New Mexico study has found that Hispanic women are more likely than white women to be diagnosed with breast cancer at a younger age, are more likely to be estrogen-receptor (ER) negative, and are at greater risk for poor survival. Diane D. Crumley, PhD, research assistant professor, Division of Epidemiology and Preventive Medicine, University of New Mexico, reported the findings at the Era of Hope Department of Defense Breast Cancer Research Program meeting.

NEW ORLEANS-Radiation therapy after mastectomy reduces locore-gional recurrence rates for breast cancer patients with positive lymph nodes, positive surgical margins, or both, according to the results of a large retrospective study presented at the 44th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO abstract 153).

ORLANDO-Women in all ethnic groups who have spent their lives exercising, performing heavy household chores, or tackling a physically strenuous job had a lower risk of breast cancer than their more sedentary counterparts, according to a poster presented at the Era of Hope Department of Defense Breast Cancer Research Program meeting. "We were pleased with the results," said principal investigator Esther M. John, PhD, director of epidemiology research, Northern California Cancer Center, Union City. "It’s a message we can give women to help prevent breast cancer, and there are other health benefits to physical activity."

BOSTON-Pegfilgrastim (Neu-lasta), the longer-lasting analog of the colony-stimulating factor filgrastim (Neupogen), is safe for elderly breast cancer patients receiving myelosuppressive chemotherapy and protects against febrile neutropenia, according to a poster presented at the third meeting of the International Society of Geriatric Oncology (SIOG abstract P-23).

In just 10 years, the cost of screening mammography litigation in the United States could top $250 million a year, a recent analysis has found. The analysis, presented at this year’s American Roentgen Ray Society meeting in Atlanta, is based on a

SEATTLE, Washington-In a new endeavor, an international group of experts is creating detailed guidelines for the screening, diagnosis, and treatment of breast cancer in countries and regions of the world with limited resources. The endeavor began with the Global Summit Consensus Conference and will lead to the publication, dissemination, and translation of the first edition of the guidelines next year.

NEW ORLEANS-Having a previous pregnancy improves the prognosis for women who develop early-stage breast cancer later in life, according to a study presented at the 44th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (abstract 152). The findings suggest that a more aggressive treatment approach should be considered for those patients who have not had a pregnancy.

RESEARCH TRIANGLE PARK, North Carolina-Researchers have begun the first phase of a long-term, prospective epidemiological study designed to determine the role of genetic, environmental, and lifestyle factors in increasing the risk of breast cancer and several other diseases. The Sister Study is the first long-term follow-up study specifically designed to look at hereditary and environmental risk factors for the disease. It seeks to enroll 50,000 cancer-free women in the United States between the ages of 35 and 74 who have a sister diagnosed with breast cancer.

During the 1990s, perhaps no other therapy for women with breast cancer was more controversial than high-dose chemotherapy with autologous bone marrow and/or peripheral stem cell support. With encouraging results from late phase I and early phase II trials in the early to mid-1990s, high-dose chemotherapy was promoted by its many enthusiastic proponents as a potentially great leap forward for women with high-risk, node-positive or metastatic disease.