Abstract
Purpose
The aim of this study was to investigate the influence of age at diagnosis of atypical hyperplasia (“atypia”, ductal [ADH], lobular [ALH], or severe ADH) on the risk of developing subsequent invasive breast cancer or ductal carcinoma in situ (DCIS).
Methods
Using standard survival analysis methods, we retrospectively analyzed 1353 women not treated with chemoprevention among a cohort of 2370 women diagnosed with atypical hyperplasia to determine the risk relationship between age at diagnosis and subsequent breast cancer.
Results
For all atypia diagnoses combined, our cohort showed a 5-, 10-, and 15-year risk of invasive breast cancer or DCIS of 0.56, 1.25, and 1.30, respectively, with no significant difference in the (65,75] year age group. For women aged (35,75] years, we observed no significant difference in the 15-year risk of invasive breast cancer or DCIS after atypical hyperplasia, although the baseline risk for a 40-year-old woman is approximately 1/8 the risk of a 70-year-old woman. The risks associated with invasive breast cancer or DCIS for women in our cohort diagnosed with ADH, severe ADH, or ALH, regardless of age, were 7.6% (95% CI 5.9–9.3%) at 5 years, 25.1% (20.7–29.2%) at 10 years, and 40.1% (32.8–46.6%) at 15 years.
Conclusion
In contrast to current risk prediction models (e.g., Gail, Tyrer-Cuzick) which assume that the risk of developing breast cancer increases in relation to age at diagnosis of atypia, we found the 15-year cancer risk in our cohort was not significantly different for women between the ages of 35 (excluded) and 75. This implies that the “hits” received by the breast tissue along the “high-risk pathway” to cancer might possibly supersede other factors such as age.
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Acknowledgement
The authors wish to acknowledge Ann S. Adams for writing and editorial assistance.
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Conflict of interest
Author Giovanni Parmigiani is a member of the Scientific Advisory Board for CRA Health; author Judy E.Garber has research funded by Myriad Genetics, leads a clinical trial for Astra-Zeneca, has a research collaboration with Ambry, and is a consultant for GTx Pharmaceutics and Helix. All the other authors declare no conflict of interests.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent: this is a data-analysis only study; this study was approved by the IRB and the informed consent process was waived as there was no direct contact with patients.
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Emanuele Mazzola and Suzanne B. Coopey contributed equally to this work.
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10549_2017_4320_MOESM1_ESM.eps
Supplementary material 1 (EPS 325 kb) Figure S1: Sensitivity analysis with 95%-confidence intervals, using all the patients not treated with chemoprevention (n=1353) subdivided into two age groups. We assume that “premenopausal” patients are aged (19,50], n=626, and “postmenopausal” patients are aged (50,93], n=727; p-value of the logrank test: 0.134. The right panel shows the same figure as the left panel, on a reduced vertical scale with confidence intervals.
10549_2017_4320_MOESM2_ESM.eps
Supplementary material 2 (EPS 334 kb) Figure S2: Sensitivity analysis with 95% confidence intervals using patients subdivided into 20-year age classes: (25,45], n=319, (45,65], n=845, (65,85], n=189; observe that age groups (19,25] and (85, 93] do not contain any individuals and they have been omitted from the analysis. The right panel shows the same figure as the left panel, on a reduced vertical scale, with confidence intervals. p-value of the logrank test: 0.295.
10549_2017_4320_MOESM3_ESM.eps
Supplementary material 3 (EPS 289 kb) Figure S3: The left panel reports, for comparison, the same picture presented as Figure 2, whereas the right panel reports the 95% confidence intervals for the younger age groups (25,35], n=38, and all the other age groups combined (35, 85], n=1315.
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Mazzola, E., Coopey, S.B., Griffin, M. et al. Reassessing risk models for atypical hyperplasia: age may not matter. Breast Cancer Res Treat 165, 285–291 (2017). https://doi.org/10.1007/s10549-017-4320-7
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DOI: https://doi.org/10.1007/s10549-017-4320-7