© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 2, 151-152,
January 17, 2001
© 2001 Oxford University Press
CORRESPONDENCE |
RESPONSE: Re: Biologic Characteristics of Interval and Screen Detected Breast Cancers
Correspondence to: Kelly-Anne Phillips, M.B.B.S, Department of Hematology and Medical Oncology, Peter MacCallum Cancer Institute, Locked Bag No 1, A'Beckett St., Victoria, 8006 Australia.
Recent articles in the Journal by Gilliland et al. (1) and Porter et al. (2) suggest that cancers that are detected in the interval between screening mammograms are more likely than mammographically detected tumors to have features, such as high tumor grade, estrogen receptor negativity, and p53 positivity. One explanation for this is that mammographically occult tumors with such features might proliferate rapidly, growing larger, and becoming palpable in the interval between mammograms. Indeed this argument has been used to suggest there is equipoise for research into the benefits and risks of reducing the time between screening examinations (1). However, an alternate hypothesis is that tumors with these features might be less easily radiographically detectable. Unfortunately, in neither of these articles is there data on whether the interval-detected tumors could be seen on diagnostic mammograms performed at the time of their clinical detection. In an attempt to address this issue, Narod et al. present data from the Ontario Breast Cancer Screening Program showing that palpable tumors not visualized by mammography were more likely to have lobular or mixed lobular histology, to be larger, and to be axillary lymph node positive. However, it is unclear from the data presented whether these features were independently statistically significant on multivariate analysis or whether the features highlighted as important in the previous articles (tumor grade, hormone receptor status, and p53 mutation status) were examined. Indeed, the major finding seems to be that lobular tumors are more likely to be mammographically occult, an observation that has been well documented previously (3,4).
It is suggested that the findings of the studies by Gilliland et al. (1) and Porter et al. (2) may have implications for mammographic screening of BRCA1 mutation carriers. BRCA1-associated breast cancers have a relatively homogeneous phenotype that generally includes high grade, p53 positivity, and estrogen receptor negativity (5). Indeed, one small study of the mammographic appearances of breast tumors from BRCA1 mutation carriers showed that palpable cancers in BRCA1 carriers are less frequently visualized on mammography than palpable tumors of age-matched control subjects (6).
Screening young BRCA1 carriers with mammography has well recognized problems, including the decreased sensitivity of the test in younger women from increased breast density. The finding that the biologic type of breast cancer usually associated with BRCA1 mutation may be less frequently detected by mammography increases concern that regular mammography may be of less value than hoped in this situation. In addition, some have voiced concern about the possibility of breast cancer induction by mammography in women who are at increased genetic risk (7), an argument that is supported by the proposed DNA repair function of BRCA1, but for which, to date, inadequate clinical data exist to support or refute.
Clearly, further studies are required to elucidate this issue, both in the general population and in women who carry mutations in cancer predisposition genes. In the meantime, some may wish to incorporate these data in the discussion about the pros and cons of various surveillance and prevention options for mutation carriers. Where possible, such women should be offered participation in trials of possible alternate screening methods such as magnetic resonance imaging.
REFERENCES
1
Gilliland FD, Joste N, Stauber PM, Hunt WC, Rosenberg R, Redlich G, et al. Biologic characteristics of interval and screen-detected breast cancers. J Natl Cancer Inst 2000;92:743–9.
2
Porter PL, El-Bastawissi AY, Mandelson MT, Lin MG, Khalid N, Watney EA, et al. Breast tumor characteristics as predictors of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst 1999;91:2020–8.
3
Ma L, Fishell E, Wright B, Hanna W, Allan S, Boyd NF. Case–control study of factors associated with failure to detect breast cancer by mammography. J Natl Cancer Inst 1992;84:781–5.
4 Holland R, Hendriks JH, Mravunac M. Mammographically occult breast cancer. A pathologic and radiologic study. Cancer 1983;52:1810–9.[CrossRef][Web of Science][Medline]cancerlit;84026081
5
Phillips KA, Andrulis IL, Goodwin PJ. Breast carcinomas arising in carriers of mutations in BRCA1 or BRCA2: are they prognostically different? J Clin Oncol 1999;17:3653–63.
6 Chang J, Yang WT, Choo HF. Mammography in Asian patients with BRCA1 mutations. Lancet 1999;353:2070–1.[Web of Science][Medline]cancerlit;99303136
7 Den Otter W, Merchant TE, Beijerinck D, Koten JW. Breast cancer induction due to mammographic screening in hereditarily affected women. Anticancer Res 1996;16:3173–5.[Web of Science][Medline]cancerlit;97096780
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