CORRESPONDENCE

RESPONSE: More About: Multifactorial Analysis of Differences Between Sporadic Breast Cancers and Cancers Involving BRCA1 and BRCA2 Mutations

Deborah L. Brown, Bernard F. Cole, Bradley A. Arrick

Affiliations of authors: Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH.

Correspondence to: Bradley A. Arrick, M.D., Ph.D., Dartmouth Medical School, Kellogg Box 0128, Hanover, NH 03755 (e-mail: Bradley.Arrick{at}dartmouth.edu).

The new data from Eisinger et al., indicating that approximately 80% of estrogen receptor-negative breast cancers from BRCA1 mutation carriers also lack expression of pS2, are a welcome addition to our knowledge base regarding BRCA1-associated tumors. In a recently published study, Armes et al. (1) report a similar concordance between absence of estrogen receptor and lack of pS2 expression in breast cancers from BRCA1 mutation carriers, although they did not observe a statistically significant difference in pS2 expression between cancers from BRCA1 mutation carriers and control subjects in their series. Perhaps most importantly, given the association between pS2 expression and responsiveness to tamoxifen (2), these data underscore the concern that antiestrogen-based strategies may be ineffectual for the majority of BRCA1 mutation carriers.

In our prior correspondence (3), we suggested that estrogen receptor expression of the breast cancer of affected family members could be used, via Bayesian analysis, to fine tune the a priori estimate of finding a pathologic mutation. Our other principal suggestion was that multifactorial prediction models be developed that incorporate discriminating elements of tumor pathology, such as hormone receptor content, that are readily available in standard pathology reports and for which there is high interobserver agreement. On this score, immunohistochemical analysis of pS2 expression would be an inappropriate component to such a model

REFERENCES

1 Armes JE, Trute L, White D, Southey MD, Hammet F, Tesoriero A, et al. Distinct molecular pathogeneses of early-onset breast cancers in BRCA1 and BRCA2 mutation carriers: a population-based study. Cancer Res 1999;59:2011-7.[Abstract/Free Full Text]

2 Soubeyran I, Quenel N, Coindre JM, Bonichon F, Durand M, Wafflart J, et al. pS2 protein: a marker improving prediction of response to neoadjuvant tamoxifen in post-menopausal breast cancer patients. Br J Cancer 1996;74:1120-5.[Medline]

3 Brown DL, Cole BF, Arrick BA. Re: Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations [letter], J Natl Cancer Inst 1999;91:90-1.[Free Full Text]



             
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