Journal of the National Cancer Institute Advance Access published online on October 7, 2008
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djn320
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© The Author 2008. Published by Oxford University Press.
ARTICLES |
Tamoxifen Chemoprevention Treatment and Time to First Diagnosis of Estrogen Receptor–Negative Breast Cancer
Affiliations of authors: Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, TX (YS); Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA (JPC); Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, MD (JQ)
Correspondence to: Yu Shen, PhD, Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1411, Houston, TX 77030-4095 (e-mail: yshen{at}mdanderson.org).
Background: Tamoxifen’s effect of reducing the risk of estrogen receptor (ER)–positive breast cancer is well established. Its effect on the time to first diagnosis of breast cancer has not been reported. We used information from the randomized, placebo-controlled Breast Cancer Prevention Trial (BCPT) to make that evaluation.
Methods: A total of 13 388 women enrolled in BCPT, of whom 174 were diagnosed with ER-positive tumors and 69 were diagnosed with ER-negative tumors. A flexible semiparametric cure rate model was used to assess the effects of tamoxifen vs placebo treatment on the time to disease diagnosis. Multivariable logistic regression, adjusted for age and tumor size at diagnosis, was used to assess the association between the mammography detection rate and treatment with tamoxifen. All statistical tests were two-sided.
Results: The median times to diagnosis of ER-positive tumors were similar in both treatment groups (43 months for the placebo arm and 51 months for the treatment arm). Times to diagnosis of ER-negative tumors, however, differed between treatment groups, with median times to diagnosis of 36 months in the placebo arm vs 24 months in the tamoxifen arm (difference = 12 months, 95% confidence interval [CI] = 3 to 17 months, P = .037). ER-negative breast cancers in the tamoxifen arm were more likely than those in the placebo arm to be detected by mammography than by clinical breast examination alone after adjustment for age and tumor size, but the increase was only marginally statistically significant (odds ratio for mammography detection = 4.68, 95% CI = 0.86 to 25.32, P = .073). No differences were found in the mammography detection rates for ER-positive tumors by treatment arm.
Conclusion: Although tamoxifen treatment does not reduce the incidence of ER-negative breast cancer, it may have advanced detection of such tumors by approximately 1 year, compared with that in the placebo arm. The time to diagnosis of ER-positive breast cancer was similar in both treatment arms.
| Context and Caveats Prior knowledge The effect of tamoxifen chemoprevention treatment on the time to first diagnosis of breast cancer has not been reported. Study design Subset analysis of data from the phase 3 randomized placebo-controlled Breast Cancer Prevention Trial (BCPT), in which 13 338 women were enrolled and of whom 174 were diagnosed with estrogen receptor (ER)-positive tumors and 69 were diagnosed with ER-negative tumors. Contribution Times to diagnosis of ER-positive tumors were similar in both tamoxifen and placebo treatment groups. Times to diagnosis of ER-negative tumors differed between treatment groups, with a median time of 36 months in the placebo group and 24 months in the tamoxifen group. ER-negative tumors in the tamoxifen group were more likely than those in the placebo group to be detected by mammography than by clinical breast examination alone. No differences were found in the mammography detection rates for ER-positive tumors by treatment group. Implication Although chemoprevention with tamoxifen does not reduce the incidence of ER-negative breast cancer, it appears to have advanced the detection of ER-negative tumors by approximately 1 year. This result warrants further investigation. Limitations Breast density was not assessed in the BCPT. The number of ER-negative breast cancers diagnosed was relative small and so conclusions that are based on these data should be interpreted with caution. From the Editors
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Manuscript received April 25, 2008; revised July 15, 2008; accepted August 4, 2008.
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J Natl Cancer Inst 2008 100: 1417.
J Natl Cancer Inst 2008 100: 1417.
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