Showing papers by "Benjamin F. Hankey published in 1996"

Recent Trends in U.S. Breast Cancer Incidence, Survival, and Mortality Rates

Abstract: Background: Clinical trials have demonstrated that use of mammographic screening and advances in therapy can improve prognosis for women with breast cancer. Purpose: We determined the trends in breast cancer mortality rates, as well as incidence and survival rates by extent of disease at diagnosis, for white women in the United States and considered whether these trends are consistent with widespread use of such beneficial medical interventions. Methods: We examined mortality data from the National Center for Health Statistics and incidence and survival data by extent of disease from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute, all stratified by patient age, using statistical-regression techniques to determine changes in the slope of trends over time. Results: The age-adjusted breast cancer mortality rate for U.S. white females dropped 6.8% from 1989 through 1993. A significant decrease in the slope of the mortality trend of approximately 2% per year was observed in every decade of age from 40 to 79 years of age. Trends in incidence rates were also similar among these age groups: localized disease rates increased rapidly from 1982 through 1987 and stabilized or increased more slowly thereafter; regional disease rates decreased after 1987; and distant disease rates have remained level over the past 20 years. Three-year relative survival rates increased steadily and significantly for both localized and regional disease from 1980 through 1989 in all ages, with no evidence of an increase in slope in the late 1980s. Implications: The decrease in the diagnosis of regional disease in the late 1980s in women over the age of 40 years likely reflects the increased use of mammography earlier in the 1980s. The increase in survival rates, particularly for regional disease, likely reflects improvements in systemic adjuvant therapy. Statistical modeling indicates that the recent drop in breast cancer mortality is too rapid to be explained only by the increased use of mammography; likewise, there has been no equivalent dramatic increase in survival rates that would implicate therapy alone. Thus, indications are that both are involved in the recent rapid decline in breast cancer mortality rates in the United States. [J Natl Cancer Instl996;88:1571-9]

Second Cancers After Adjuvant Tamoxifen Therapy for Breast Cancer

Abstract: Since the early 1980s, adjuvant tamoxifen therapy has been commonly used in the treatment of early stage breast cancer to improve survival and to reduce the incidence of contralateral breast cancer among postmenopausal women (1). However, the estrogenic effect of tamoxifen on the uterus (2) has been reported to increase the risk of uterine corpus cancer by twofold to threefold (3-6). Recently, an elevated risk of gastrointestinal cancer, particularly colorectal and stomach cancers, was associated with tamoxifen therapy in clinical trials (7). Because late effects of tamoxifen could adversely affect the risk-benefit ratio in ongoing chemoprevention trials, we evaluated the risk of second cancers among 87 323 women with breast cancer reported to the Surveillance, Epidemiology, and End Results (SEER) Program (8). To select women who were most likely to have received tamoxifen, we included patients with breast cancer who were 50 years of age or older, who were diagnosed with early stage disease (i.e., localized or regional) from 1980 through 1992, and who survived at least 2 months (n = 101 930). Since many women given chemotherapy also received steroids, which are classified as hormones in SEER, we excluded those individuals from the analysis (n = 14 607). Of the remaining 87 323 women, 14 358 were known to have received hormones for their first course of therapy (designated as the tamoxifen group, since approximately 90%-95% of these patients received tamoxifen [Hankey B, Harlan L: personal communication]), whereas 72 965 women were not known to have received hormones (the no/unknown tamoxifen group). Observed-toexpected ratios (O/E) of second cancers were calculated using standard methods (9,10). Patients with breast cancer initially treated with tamoxifen developed second cancers at a rate slightly higher than that expected in the general population (O/E =1.12; 95% confidence interval [CI] = 1.03-1.21) and identical to that experienced by patients with no/unknown tamoxifen therapy (O/E = 1.12; 95% CI = 1.09-1.15) (Table 1). Significant excesses of uterine corpus cancer were seen in both treatment groups, with higher risks following tamoxifen therapy (O/E = 2.03; 95% CI = 1.592.55 versus O/E = 1.23; 95% CI = 1.111.36). We observed little difference in the severity of grade or stage of uterine corpus cancer on the basis of initial therapy (Table 1), in contrast with a previous report suggesting a tendency toward higher grade lesions following tamoxifen treatment (11). Of the 73 women who developed uterine corpus cancer after tamoxifen therapy, six died of this cancer. The actuarial risk of uterine corpus cancer among postmenopausal women after adjuvant tamoxifen therapy was 1.8% at 10 years, compared with 0.9% expected in the general population. Cancers of the colon and rectum were not in excess following tamoxifen therapy (O/E = 1.04; 95% CI = 0.831.30 and O/E = 1.02; 95% CI = 0.661.49, respectively), and stomach cancer was not significantly increased (O/E = 1.23; 95% CI = 0.69-2.03), in contrast svith the findings of a recent report (7). Tamoxifen therapy appeared to decrease the risk of contralateral breast cancer (O/E= 1.12; 95% CI = 0.96-1.30 versus O/E = 1.62; 95% CI = 1.55-1.69), and a more detailed report of this result is planned. Women in the no/unknown tamoxifen group had a statistically significant lower risk of leukemia and of cancers of the liver, lung, and brain (Table 1). To sharpen the treatment comparisons, we evaluated a subgroup of women for whom adjuvant tamoxifen was infrequently used, so that misclassification of therapy would be small. Among 17 952 patients with localized breast cancer initially treated between 1980 and 1984, the risk of uterine corpus cancer was nearly identical to that experienced in the general population (O = 121 and O/E = 0.99; 95% CI = 0.82-1.19). This finding suggests that at least part of the excess risk observed in the no/unknown tamoxifen group is related to tamoxifen therapy not reported to the SEER Program. Among tamoxifen-treated patients, the risk of all second cancers, excluding contralateral breast cancer, was significantly increased among survivors of 5 or more years (O/E = 1.32; 95% CI = 1.02-1.68), whereas no excess cancer risk was found for the no/unknown tamoxifen group in this follow-up interval (O/E = 0.96; 95% CI = 0.90-1.02) (Table 2). A notable increase in uterine corpus cancer (O/E = 3.59; 95% CI = 1.96-6.02) and a nonsignificant excess of stomach cancer (four cases; O/E = 2.61; 95% CI = 0.70-6.69) were observed 5 years or more after breast cancer diagnosis among women who received tamoxifen therapy. Although the number of patients with breast cancer evaluated in this study is large, few tamoxifen-treated patients have been followed for more than 10 years, limiting our ability to evaluate long-term survivors. Other limitations include a lack of detailed information on initial and subsequent therapy and an absence of data on other factors affecting second cancer risk, such as menopausal estrogen use and hysterectomy. Our results support the link between tamoxifen therapy and subsequent de-

Second Malignant Neoplasms among Long-Term Survivors of Ovarian Cancer

Abstract: Second malignant neoplasms were evaluated among 32,251 women with ovarian cancer, including 4,402 10-year survivors, within the nine population-based registries of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute (1973-1992) and the Connecticut Tumor Registry (1935-1972). Overall, 1,296 second cancers occurred against 1,014 expected [observed/expected (O/E), 1.28; 95% confidence interval (CI), 1.21-1.35]. Sites contributing 25 or more excess cancers included leukemia (O/E, 4.17; O, 111; 95% CI, 3.43-5.03) and malignancies of colon (O/E, 1.33; O, 188; 95% CI, 1.15-1.54), rectum (O/E, 1.43; O, 76; 95% CI, 1.13-1.79), breast (O/E, 1.18; O, 404; 95%, CI 1.07-1.30), and bladder (O/E, 2.07; O, 65; 95% CI, 1.59-2.63). Ocular melanoma (O/E, 4.45; O, 8; 95% CI, 1.92-8.77) was also significantly increased. Second cancer risk was high during all follow-up intervals, and cumulative risk at 20 years was 18.2%, compared with a population expected risk of 11.5%. Statistically significant relationships existed between serous adenocarcinoma of the ovary and breast cancer (O/E, 1.29; 95% CI, 1.06-1.56) and mucinous ovarian adenocarcinoma and rectal cancer (OE/E, 1.95; 95% CI, 1.09-3.22). Secondary leukemia appeared linked with antecedent chemotherapy, whereas radiotherapy was associated with cancers of connective tissue, bladder, and possibly pancreas. Genetic and reproductive factors predisposing to ovarian cancer may have contributed to the elevated risk of breast and colorectal neoplasms and possibly ocular melanoma. Thus, excess malignancies following ovarian cancer represent complications of curative therapies and/or underlying susceptibility states that have etiological and clinical ramifications.

Prognostic significance of in situ carcinoma associated with invasive breast carcinoma. A natural experiment in cancer immunology

Abstract: BACKGROUND. Our previous studies indicate that the in situ phase of mammary carcinogenesis is characteristically associated with cell-mediated immunity (CMI) against an immunogen shared by most breast carcinomas. Such reactivity is inversely correlated with stage and appears to impede in situ-to-invasive progression and lethality from invasive breast carcinoma. If in situ carcinomas are indeed associated with ambient, prognostically favorable immunity against such an immunogen, one would expect lethality from invasive breast carcinoma to be reduced in patients with a diagnosis of a prior, simultaneous, or subsequent in situ breast carcinoma. The present study provides a test of such relationships. METHODS. Patient survival was analyzed for 129,394 female patients with invasive breast carcinoma diagnosed in areas covered by the Surveillance, Epidemiology, and End Results (SEER) Program based at the National Cancer Institute (NCI). Patients were classified according to whether they had a prior, simultaneous, or subsequent in situ breast carcinoma and survival was examined for up to 15 years subsequent to diagnosis using life tables and the Cox regression model. RESULTS. The findings indicate that patients with an invasive breast carcinoma who had a prior, simultaneous, or subsequent in situ breast carcinoma did experience significantly better survival than comparison groups of patients who either did not have an associated cancer of any type, had an associated invasive breast carcinoma, or had an in situ or invasive cancer of non-breast origin. CONCLUSIONS. Our prior and current observations warrant more direct studies of the prognostic, therapeutic, and prophylactic significance of the in situ carcinomaassociated type of specific CMI in breast cancer patients.