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Breast Cancer

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SOUTHAMPTON PRINCESS, Bermuda-Three large randomized studies comparing the antiestrogens toremifene (Fareston) and tamoxifen (Nolvadex) in patients with advanced breast cancer showed no significant differences in efficacy or toxicity, Richard A. Gams, MD, of the James Cancer Hospital, Ohio State University, said at a symposium on antiestrogen therapy for breast cancer sponsored by Schering.

ATLANTA-With 8 million new breast cancer patients each year worldwide, “we’re looking at a tremendous number of individuals being followed for recurrence,” Hyman B. Muss, MD, of Fletcher Allen Health Care, Burlington, Vermont, said at the Perspectives in Breast Cancer symposium.

It is not often that a reviewer agrees entirely with material presented in an article. I find myself in the happy situation of largely agreeing with the basic thrust of this interesting report by Chadha and Axelrod. They begin by describing the increased incidence of breast cancer over the recent decade, but do not mention that since 1990 there has actually been a decreased incidence of breast cancer.[1] In retrospect, it has become clear that the statistical increase in breast cancer during the 1980s was an artifact of extensive mammographic screening, which caught the initial appearance of disease earlier and artificially created a temporary surge of cases that has since abated.[2]

Although the article by Senie and Tenser reviewing some of the data relevant to whether operative timing within the menstrual cycle affects breast cancer outcome is reminiscent of a recent paper that appeared in the December 1996 issue of the Journal of Women’s Health,[1] the question it considers is potentially important enough that this issue should also be raised in Oncology. The article points out the experimental basis for believing that an important interaction may occur between the host-cancer-surgery and the mammalian reproductive cycle.[2,3] This is an important supposition because clinicians have routinely assumed that no experimental foundation underlaid the first and 31 subsequent analyses of relevant clinical data[4,5]-an assumption that is false.

The authors provide a comprehensive overview of the role of axillary lymphadenectomy in the treatment of early-stage breast cancer. They do not argue against lymphadenectomy for patients with clinical T2 and 3 tumors and clinical N1 and 2 nodes. However, for clinical N0 cancers and for postmenopausal patients with hormone-receptor-positive tumors, the authors propose radiotherapy to the axilla as a modality less expensive than surgery and with fewer complications. They suggest observation only for lesions associated with a less than 10% to 15% chance of axillary metastasis (T1a cancers, tubular carcinomas, ductal carcinoma in situ [DCIS] with microinvasion). However, for patients with lesionsless than 1 cm with “high-risk features (presence of tumor emboli in vessels, poor nuclear grade, etc),” axillary lymphadenectomy “should continue to serve as a refined prognostic indicator for selection of patients for adjuvant therapy.”

The discussions and debates about the use of estrogen replacement therapy (ERT) in women with breast cancer often seem to ignore or at least leave unnoted the extensive data supporting the general premise that increased, but physiologic levels of estrogens are associated with poorer survival in postmenopausal women with breast cancer. Dr. Colditz summarizes various lines of evidence bolstering this general premise, providing us with some needed lessons about the complexities of interpreting epidemiologic studies and about human cancer biology. Particularly illuminating are his discussion of the biases in ERT-breast cancer causation studies and his exploration of the reasons for the apparently better survival in ERT users who develop breast cancer.

Dr. Colditz has reviewed the potential hazards of hormone replacement therapy in breast cancer survivors. Let us presume, for the sake of brevity, that his assumptions are correct. With so many risks, why would a breast cancer survivor consider taking hormone replacement, and why would an oncologist prescribe it?

Contemporary breast cancer treatment research has focused on systemic postoperative adjuvant treatment and the elimination of established micrometastases. An alternative approach addresses the potential for seeding at the time of primary surgery. Several retrospective reports have suggested that the hormonal milieu during lumpectomy or mastectomy impacts on the likelihood of tumor cell shedding and implantation at distant sites.

SAN DIEGO-Breast cancer patients with an inherited predisposition due to mutations of BRCA1 or BRCA2 are more likely to have an accumulation of other genetic defects than patients with no evidence of a familial clustering, according to a multinational study, said Mika Tirkkonen, of the University of Tampere, Finland.