CORRESPONDENCE

Re: Risk of Subsequent Cancer Following Breast Cancer in Men

Kari Hemminki, Charlotta Granström

Affiliations of authors: K. Hemminki, Department of Biosciences at Novum, Karolinska Institute, Huddinge, Sweden, and Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; C. Granström, Department of Biosciences at Novum, Karolinska Institute, Huddinge.

Correspondence to: Kari Hemminki, M.D., Ph.D., CNT Novum, 141 57, Sweden (e-mail: kari. hemminki{at}cnt.ki.se).

Auvinen et al. (1) published results on male breast cancer based on the Surveillance, Epidemiology, and End Results (SEER)1 data source. They showed a standardized incidence ratio (SIR) for contralateral breast cancer of 29.64 in 12 individuals. Melanoma was also in excess after breast cancer (SIR = 2.41). However, when breast cancer was analyzed as a second primary cancer after any other type of cancer, no statistically significant increases were observed.

In 2001, we published a study of male breast cancer, in which we showed an SIR for second primary breast cancer to be 93.1 (N = 8, 95% confidence interval [CI] = 39.8 to 184.3) (2). We had no information on laterality, but the SIR was highest (111.7) 10 to 38 years after the first breast cancer, suggesting that the second cancer was not a recurrence of the first cancer. The data were derived from the 1999 update of the Swedish Family-Cancer Database [see supplementary information to reference (3) for more information on the Database]. However, we did not study other cancers that appeared after the first breast cancer.

Here, we determined SIRs for first and second primary male breast cancer and for first breast cancer in daughters of male probands from a more recent update of the Swedish Family-Cancer Database, covering the years 1961 through 1998 (3). Follow-up for second primary cancer began at the time of diagnosis of the first primary cancer and provided the observed number of cases. Expected numbers of cases were obtained from the corresponding population in the Database. SIRs were adjusted for age, time period, geographic region, and socioeconomic status, and data on females were also adjusted for parity and age at first birth.

We derived SIRs for some common cancers that were diagnosed after first male breast cancer (N = 552) and for breast cancer that was diagnosed after any other primary cancer (Table 1Go), similar to the analysis by Auvinen et al. (1). Although we had no data on laterality, the risk of breast cancer was increased after a first breast cancer to 112.2 (n = 12, 95% CI = 57.7 to 184.6). We next analyzed the risk relative to the time of the first diagnosis: less than 1 year after, SIR = 176.5 (n = 3, 95% CI = 33.3 to 432.7); 1 to 10 years after, SIR = 84.9 (n = 6, 95% CI = 30.5 to 166.4); and more than 10 years after, SIR = 155.4 (n = 3, 95% CI = 29.3 to 381.1). After a first breast cancer, there were more prostate cancers than expected (SIR = 1.6, 95% CI = 1.0 to 2.3), but the increase in the number of melanomas was not statistically significant (SIR = 1.8, 95% CI = 0.2 to 5.0). There was no increase in subsequent breast cancer after any other cancer. Because we had information on all family members, we calculated familial risk for breast cancer in daughters of men with breast cancer compared with all daughters. If a father had a single breast cancer, then the SIR for a daughter was 1.5 (N = 13, 95% CI = 0.8 to 2.6), but if a father had two breast cancers, then the SIR for a daughter was 10.3 (N = 2, 95% CI = 1.0 to 37.9). This high SIR, which is of borderline statistical significance, suggests that multiple breast cancers in men are indicative of a familial risk, in agreement with female breast cancer (4) and many other types of cancer (5,6). Because of the rarity of male breast cancer, even nationwide studies have low statistical power. However, the familial risks and the clustering of male breast cancer with prostate cancer and melanoma suggest possible involvement of BRCA2 mutations (7).


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Table 1. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for second cancers after male breast cancer and for second breast cancer after any other cancer in the Swedish Family-Cancer Database*
 

NOTES

Auvinen et al. declined to respond to the correspondence by Hemminki and Granström.

1 SEER is a set of geographically defined, population-based, central cancer registries in the United States, operated by local nonprofit organizations under contract to the National Cancer Institute (NCI). Registry data are submitted electronically without personal identifiers to the NCI on a biannual basis, and the NCI makes the data available to the public for scientific research. Back

REFERENCES

1 Auvinen A, Curtis R, Ron E. Risk of subsequent cancer following breast cancer in men. J Natl Cancer Inst 2002;94:1330–2.[Abstract/Free Full Text]

2 Dong C, Hemminki K. Second primary breast cancer in men. Breast Cancer Res Treat 2001;66:171–2.[Medline]

3 Hemminki K, Granström C. Risk for familial breast cancer increases with age. Nat Genet 2002;32:233.[Medline]

4 Vaittinen P, Hemminki K. Risk factors and age-incidence relationships for contralateral breast cancer. Int J Cancer 2000;88:998–1002.[Medline]

5 Dong C, Hemminki K. Multiple primary cancers at colon, breast and skin (melanoma) as models for polygenic cancers. Int J Cancer 2001;92:883–7.[Medline]

6 Hemminki K, Boffetta P. Multiple primary cancers as clues of environmental and heritable causes of cancer and of mechanisms of carcinogenesis. IARC Sci Publ. In press 2002.

7 Cancer risks in BRCA2 mutation carriers. The Breast Cancer Linkage Consortium. J Natl Cancer Inst 1999;91:1310–6.[Abstract/Free Full Text]



             
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