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Approximately 25% of patients with stage I (node negative) breast cancer relapse at a rate similar to those with stage II disease. Inadvertent pathologic "understaging" of lymph node status is one plausible explanation for this phenomenon. While many studies have shown that additional sectioning +/- immunohistochemical staining for epithelial markers increases the rate of detection of small deposits of metastatic carcinoma, few have had sufficient statistical power to examine the impact of "occult" metastasis on clinical outcome. This provocative update by the International Ludwig Breast Cancer Study Group provides support for considering going "the extra mile" to detect lymph node metastasis in postmenopausal patients and those with the lobular subtype of invasive breast cancer.

Objective: To estimate by meta-analysis the risk of developing cancer of the breast, uterine cervix, endometrium, ovary, and liver from age 20-54 years in the United States in women using oral contraceptives (OCs) for 4, 8, or 12 years., Data Sources: Using pairs of terms (such as oral contraception and breast neoplasms), I searched for English-language literature on OC use and cancer published since 1980 and cited through July 1994 in the MEDLINE data base., Methods of Study Selection: I analyzed all epidemiologic studies reporting estimates of relative risk (RR) by duration and recency of OC use (79 independent studies in total)., Data Extraction and Synthesis: Reported duration-specific and recency-specific estimates of RR, with the corresponding numbers of cases and controls or person-time at risk for cohort studies, were abstracted from each article. Relative risk of cancer as a function of both duration and recency of OC use was then estimated by weighted regression and applied, using life-table methods, to United States population-based data on age-specific mortality and cancer incidence., Conclusions: For every 100,000 women in the United States who never use OCs, the number developing cancer from age 20-54 years is estimated to be 2782 (breast), 425 (cervix), 438 (endometrium), 369 (ovary), and 20 (liver). For women using OCs for 8 years, the estimated number of additional or fewer cases per 100,000 users is +151 (breast), +125 (cervix), -197 (endometrium), -193 (ovary), and +41 (liver). Therefore, from a population perspective, there are only small cancer-related risks and benefits associated with OC use and, on balance, the net effect is negligible.

Objective: To determine the effect of oral contraceptive (OC) use on the cumulative incidence of epithelial ovarian cancer from ages 20-40, 20-50, and 20-55 years among four groups of women: positive family history, negative family history, parous, and nulliparous., Methods: Cancer and Steroid Hormone Study data were combined with data from the Surveillance, Epidemiology, and End Results Network to provide estimates of the age-specific incidence rates of epithelial ovarian cancer among never-users of OCs in the four specified groups of women. These rates provided the basis for calculating cumulative incidences. The rates in women using OCs were estimated from meta-analyses of the epidemiologic literature, using regression equations expressing the log-relative rate of epithelial ovarian cancer as a function of duration of use and recency., Results: In all four groups, the cumulative number of epithelial ovarian cancer cases estimated to occur per 100,000 OC users, compared to never-users, decreased with increasing duration of OC use. Our results suggest that 5 years of OC use by nulliparous women can reduce their ovarian cancer risk to the level seen in parous women who never use OCs, and that 10 years of OC use by women with a positive family history can reduce their risk to a level below that for women whose family history is negative and who never use OCs., Conclusion: These data represent the first published estimates of the effect of OC use on the cumulative incidence of epithelial ovarian cancer by family history and by parity. The demonstrated substantial noncontraceptive benefit from OCs justifies their judicious use as a potentially powerful resource for primary prevention in women at high risk of ovarian cancer.