Breast Cancer

SEATTLE--"Is it possible that at some point in human evolution, there was some selective advantage of BRCA1 and BRCA2?" Mary-Claire King, PhD, asked during her presentation at the annual meeting of the American Association for the Advancement of Science (AAAS).

Response to liarozole fumarate has been observed in patients with receptor-positive metastatic breast cancer, as well as those with receptor-unknown disease, confirming the biologic efficacy of this agent. The first clinical study of the role of liarozole in

PALM SPRINGS, Calif--Data from preclinical studies of the antiestro-gen agent toremifene (Fareston), and their correlation with data from clinical studies, may provide information useful in designing trials comparing toremifene with tamoxifen (Nolvadex) as adjuvant breast cancer therapy, Michael DeGregorio, PharmD, said at the symposium.

The controversies regarding the association between hormonal replacement therapy (HRT) and cancers, the questions about HRT use in women with a high risk of breast cancer, and the increasing number of women with breast cancer and menopausal symptoms make HRT a significant cancer issue.

Overexpression by the HER2 gene plays a significant role in breast cancer pathogenesis, and the phenomenon is commonly regarded as a predictor of a poor prognosis. HER2 overexpression has been linked to sensitivity and/or resistance to hormone therapy and chemotherapeutic regimens, including CMF (cyclophosphamide, methotrexate, and fluoro-uracil) and anthracyclines. Studies of patients with advanced disease demonstrate that, despite the association of HER2 overexpression with poor prognosis, the odds of HER2-positive patients responding clinically to taxanes were greater than three times those of HER2-negative patients. Further studies in preclinical models used combination therapy for breast cancer cells that overexpress HER2, and the use of agents that interfere with HER2 function plus paclitaxel (Taxol) resulted in significant antitumor effects. [ONCOLOGY 11(Suppl):43-48, 1997]

Clinical trials to develop paclitaxel (Taxol)-containing combinations started in 1992 with several approaches to combine doxorubicin and paclitaxel. Schedule-dependent toxicity limited doses in the initial trials, although antitumor activity was high. More recently, a well-tolerated, highly effective doxorubicin/paclitaxel regimen was developed with the use of bolus anthracycline administration and a 3-hour infusion of paclitaxel. Combinations of paclitaxel with cisplatin have provided mixed results. Paclitaxel combined with fluorouracil (5-FU) and folinic acid proved effective in patients with extensive prior chemotherapy; the addition of mitoxantrone (Novantrone) to this combination was feasible, well tolerated, and possibly enhanced the efficacy of paclitaxel and 5-FU. Combinations of paclitaxel with cyclophosphamide (Cytoxan, Neosar), vinorelbine (Navelbine), edatrexate, and radiation continue in clinical development. [ONCOLOGY 11(Suppl):29-37, 1997]

The following position statement was made by the American Association for Cancer Research in response to the press release on mammography screening for women 40 to 49 years old issued by the National Institutes of Health

The proven safety profile and antitumor activity of paclitaxel (Taxol) in the treatment of metastatic breast cancer led investigators at Memorial Sloan-Kettering Cancer Center (MSKCC) to further examine the agent's potential in the treatment of advanced breast cancer. Efficacy and tolerability studies of paclitaxel as single-agent therapy were undertaken, along with parallel investigations of quality-of-life parameters. The studies examined the effects of 96-hour infusion schedules of paclitaxel and are currently assessing the feasibility of a weekly 1-hour infusion schedule. Researchers at MSKCC also compared the results of a variety of two- and three-drug paclitaxel-containing regimens to determine possible synergism and better define safety profiles. They examined the combination of paclitaxel and edatrexate, as well as a promising combination of paclitaxel and a monoclonal antibody directed at growth factor receptors. The latter ongoing trial will include both laboratory studies that examine possible cellular mechanisms for the combination's observed synergy and a clinical trial that combines paclitaxel with a monoclonal antibody directed against the epidermal growth factor. In conclusion, the investigators discuss the optimal integration of paclitaxel into doxorubicin/cyclophosphamide (Cytoxan, Neosar)-based adjuvant therapy for node-positive stage II-III resectable breast cancer. [ONCOLOGY 11(Suppl):20-28, 1997]

The extensively studied agent docetaxel (Taxotere) has shown marked clinical activity in the treatment of anthracycline-resistant breast cancer. Phase I trials indicate that toxicities, such as mucositis and neutropenia, limit the administration of docetaxel to shorter perfusion schedules. Pharmacokinetic studies have shown that docetaxel's clearance by hepatic metabolism is correlated with a marked increase in risk of toxicity in patients with impaired liver function. Nevertheless, studies of docetaxel as front-line therapy for breast cancer were initiated because of its good activity against tumors in early studies and its close relationship to paclitaxel (Taxol), an agent with proven efficacy. Phase II studies have demonstrated excellent activity for docetaxel as a single agent, with an overall response rate of 61% in trials of a 100-mg/m² dose. A phase III study is currently comparing docetaxel with paclitaxel as single-agent therapy. Docetaxel is expected to provide a better response rate but a higher incidence of neutropenia. The agent shows promise in adjuvant therapy, with very high response rates in anthracycline-resistant patients. Preliminary results of tests using docetaxel in combination with doxorubicin show high objective response rates but low complete response rates; early results suggest that this combination may have some advantages over paclitaxel/doxorubicin. [ONCOLOGY 11(Suppl):38-42, 1997]

Despite the results of the National Surgical Adjuvant Breast and Bowel Project B-17, there continues to be debate regarding the most appropriate treatment for patients with ductal carcinoma in situ (DCIS) of the breast. Numerous clinical, pathologic, and laboratory factors can aid clinicians and patients wrestling with the difficult

Dr. Fowble's well-written review concludes that, in certain subgroups of patients with breast cancer (ie, patients with primary tumors larger than 5 cm, four or more positive axillary lymph nodes, or tumor involvement of the pectoralis fascia),

CHICAGO-Medical contraindications to breast-preserving cancer surgery occur in a minority of patients with early-stage breast cancer when accepted clinical guidelines are appropriately applied, results from a series of more than 400 patients suggest.

SAN FRANCISCO-A new analysis based on SEER data shows a very low probability of fatal breast cancer among women with DCIS for up to 10 years after diagnosis and treatment. Further, the data suggest that women with DCIS are, overall, healthier than the general population, Virginia L. Ernster, PhD, reported at a poster session of the San Antonio Breast Cancer Symposium.

HEIDELBERG, Germany-Evaluation of bone marrow for breast cancer cells proved superior to axillary lymph node dissection in predicting subsequent metastases in a German study of more than 1,000 patients, Ingo J. Diel, MD, said at a general session of the San Antonio Breast Cancer Symposium.

SAN ANTONIO-Most breast cancer patients vastly overestimate the benefits of adjuvant chemotherapy, believing that it reduces their risk of recurrence by as much as 77%, Laura Siminoff, PhD, reported at a general session of the San Antonio Breast Cancer Symposium.

VIENNA--The fourth-generation aromatase inhibitor letrozole has become the first drug of its class to outperform megestrol acetate as a second-line hormonal therapy for postmenopausal women with metastatic breast cancer who relapsed or progressed during tamoxifen (Nolvadex) therapy.

SAN ANTONIO-Is adjuvant radiotherapy necessary for all breast cancer patients undergoing breast-conserving therapy? Prospective, randomized studies from the NSABP indicate that it is, Norman Wolmark, MD, said in a minisymposium held in conjunction with the San Antonio Breast Cancer meeting.

Within the last 25 years, laboratory research on estrogen receptors and the development of the antiestrogen tamoxifen has dramatically refined and expanded the role of hormonal therapy in the treatment of breast cancer. An assessment of antiestrogens and their role in breast cancer therapy clinical practice was the focus of a roundtable symposium entitled "Antiestrogens: Past, Present, and Future," held in July 1996. The articles compiled in this supplement detail the discussions at the meeting of significant issues related to antiestrogen therapy, including patient selection, duration of treatment, secondary effects, and development of new antiestrogenic compounds.

ATLANTA-A study of more than 400,000 postmenopausal women has found no increased risk of fatal breast cancer with use of estrogen replacement therapy (ERT). In fact, women who reported ever having used estrogen actually had a 16% decreased risk of dying of breast cancer, Dawn Willis, PhD, MPH, reported for the American Cancer Society (ACS) at a general session of the San Antonio Breast Cancer Symposium.

PALM SPRINGS, Calif--Three major randomized trials comparing the antiestrogens toremifene (Fareston) and tamoxifen (Nolvadex) in patients with advanced breast cancer showed no significant differences in efficacy or side effects profiles, Richard Gams, MD, of Ohio State University, said at the symposium.

NEW YORK-Paclitaxel (Taxol) given as a weekly one-hour infusion has significant activity in metastatic breast cancer and is well tolerated at a dose of 100 mg/m²/wk or less, researchers from Memorial Sloan-Kettering Cancer Center reported at a poster session of the San Antonio Breast Cancer Symposium.

A group of French scientists concluded that oral vinorelbine (Navelbine) administered at a weekly dose of 80 mg/m² is well tolerated by patients with advanced breast cancer. While intravenous vinorelbine has previously proven to be highly effective

SAN ANTONIO-At almost three years' median follow-up, disease-free survival is 81% among a group of 42 women with resected breast cancer and four or more positive nodes who received dose-dense sequential chemotherapy using doxorubicin, paclitaxel (Taxol), and cyclophosphamide, Clifford A. Hudis, MD, said in his poster presentation.

ROME, Italy-The combination of paclitaxel (Taxol), fluorouracil (5-FU), and leucovorin, with G-CSF support, in pretreated patients with advanced breast cancer had a good toxicity profile and an encouraging response rate in a study from the Regina Elena Cancer Institute, Rome.

SAN ANTONIO--Two poster presentations at the San Antonio Breast Cancer Symposium suggest that breast tumors are more aggressive in African-American women than in Caucasian women.

DUARTE, Calif-Researchers at the City of Hope National Medical Center are in the process of updating their high-dose chemotherapy regimens for high-risk breast cancer patients to include paclitaxel (Taxol), George Somlo, MD, said in a poster presentation at the San Antonio Breast Cancer Symposium.

NOTTINGHAM, UK-Stable disease appears to be a clinically relevant category for judging the effectiveness of hormonal therapy in metastatic breast cancer, John Robertson, MD, said in his poster presentation of a study from the Department of Surgery, City Hospital, Nottingham.

NASHVILLE-In 1996, delivery difficulties were the major barrier to breast cancer gene therapy, Jeffrey T. Holt, MD, said at a plenary session of the San Antonio Breast Cancer Symposium.

SAN ANTONIO--Bisphosphon-ates are indicated in patients with established bone metastases from breast cancer or myeloma, to reduce skeletal complications, Alexander H.G. Paterson, MD, said at a minisymposium held in conjunction with the San Antonio Breast Cancer Symposium.

BOULOGNE, France-An oral formulation of vinorelbine (Navelbine) demonstrated encouraging antitumor activity and proved to be well tolerated in a phase I study of patients with advanced breast cancer, French physicians reported in a poster presentation.