CORRESPONDENCE

Re: Estrogen Receptor Status of Primary Breast Cancer Is Predictive of Estrogen Receptor Status of Contralateral Breast Cancer

William D. Foulkes

Correspondence to: William D. Foulkes, MB, PhD, Program in Cancer Genetics, McGill University, Montreal General Hospital, 1650 Cedar, Rm. L10-116, Montreal, Quebec, Canada H3G 1A4 (e-mail: william.foulkes{at}mcgill.ca)

The recent paper by Swain et al. (1) showing a high degree of concordance between the estrogen receptor (ER) status of first primary and contralateral breast cancers is of considerable biological interest, particularly because gene expression studies have shown that a large number of genes distinguish ER-positive from ER-negative breast cancers (2,3). In the study by Swain et al., only women diagnosed before the age of 50 did not receive tamoxifen. Thus, only in that group of women can the biology of the two breast cancers be truly studied. Notably, concordance was seen in 50 of the 62 pairs of cancers in this group of women (in 19 women, both cancers were ER negative, and in 31 women, both cancers were ER positive), leaving only 12 women (eight women with an ER-negative first cancer and an ER-positive second cancer and four women with an ER-positive first cancer and an ER-negative second cancer) in which the first and second cancers were discordant for ER status. The median time from randomization to contralateral invasive breast cancer was 4.66 years (range = 0.26–10.3 years).

It has been known for several years that, as the age at diagnosis of breast cancer increases, the probability of the tumor being ER positive increases (4). We recently quantified this phenomenon (5). For example, on the basis of the regression slope shown in Fig. 1, the percentage of ER-positive breast cancers in an unselected population increased from 62% at age 35 or younger (95% confidence interval [CI] = 55% to 69%) to 72% (95% CI = 69% to 76%) by age 49. To better understand the interplay of age and common etiologic factors that underlie the two breast cancers, it would be interesting to see how the concordance of ER status of the two cancers changes with time since first breast cancer diagnosis in the dataset analyzed by Swain et al. (1). From both our (5) and previous (6,7) data, I predict that the median interval between the first and second cancers will be shorter for the 19 women in which the two cancers were concordantly ER negative than for the women in which the two cancers were either concordantly ER positive (n = 31) or discordantly ER negative and then ER positive (n = 8). This conjecture is supported by the data from Swain et al. (1), in which only four of 62 (6%) pairs of cancers had a discordant ER-positive first/ER-negative second status, which is against the time trends (i.e., insofar as older women tend to develop ER-positive cancers) presented in Fig. 1. If confirmed, these findings would indicate that temporal factors have to be controlled for when considering concordance data. Moreover, if cancers farther apart in time are less likely to be concordant than synchronous cancers, then this suggests that pairs of first primary and contralateral cancers are composed of several different etiologically unrelated subgroups, although they were previously considered to represent a single group. Conversely, if there is no relationship between the median time interval between the first primary and contralateral breast cancer and the ER status of the two cancers, then this would imply that there is likely to be an unknown, time-insensitive factor that is playing a major role in determining the observed concordance.



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Fig. 1. Change in estrogen receptor status with increasing age at diagnosis in 596 women with invasive breast cancer. The mean percent of estrogen receptor (ER)-positive tumors (y-axis) was plotted against age at diagnosis (x-axis) for 596 women diagnosed, between 1987 and 1997, with invasive breast cancer before the age of 65 years at a single Toronto institution. The ER status of breast tumors (positive or negative), diagnosed at each age shown, was averaged (solid diamonds). ER status determination was based on a biochemical assay, and a level greater than 10 fmol/mg of protein was recorded as positive. Because 31 of 596 women were diagnosed before the age of 35 years, the data were pooled together and the mean percent ER-positive tumors for these women is shown at age 35. The best fitting slope is shown, and the 95% confidence intervals are indicated by dotted lines. R2 = 0.30; {alpha} = 0.37 (P<.001); {beta} = .007 (P = .002). The figure is based on data from reference (5).

 

NOTES

I thank Ping Sun, PhD, for statistical assistance.

REFERENCES

1 Swain S, Wilson JW, Mamounas EP, Bryant J, Wickerham LD, Fisher B, et al. Estrogen receptor status of primary breast cancer is predictive of estrogen receptor status of contralateral breast cancer. J Natl Cancer Inst 2004;96:516–23.[Abstract/Free Full Text]

2 Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature 2000;406:747–52.[CrossRef][ISI][Medline]

3 Gruvberger S, Ringner M, Chen YD, Panavally S, Saal LH, Borg A, et al. Estrogen receptor status in breast cancer is associated with remarkably distinct gene expression patterns. Cancer Res 2001;61:5979–84.[Abstract/Free Full Text]

4 Thorpe SM. Estrogen and progesterone receptor determinations in breast cancer. Technology, biology and clinical significance. Acta Oncol 1988;27:1–19.[ISI][Medline]

5 Foulkes WD, Metcalfe K, Sun P, Hanna WM, Lynch HT, Ghadirian P, et al. Estrogen receptor status in BRCA1- and BRCA2-related breast cancer: the influence of age, grade, and histological type. Clin Cancer Res 2004;10:2029–34.[Abstract/Free Full Text]

6 Kiang DT, Kennedy BJ, Snover DC. Biological and histological characteristics of simultaneous bilateral breast cancer. Lancet 1980;2:1105–7.[CrossRef][Medline]

7 Coradini D, Oriana S, Mariani L, Miceli R, Bresciani G, Marubini E, et al. Is steroid receptor profile in contralateral breast cancer a marker of independence of the corresponding primary tumour? Eur J Cancer 1998;34:825–30.[CrossRef][ISI][Medline]



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