CORRESPONDENCE

Re: Italian Randomized Trial Among Women With Hysterectomy: Tamoxifen and Hormone-Dependent Breast Cancer in High-Risk Women

Rupa Narasimhadevara, Michael N. Pollak, William D. Foulkes

Affiliations of authors: R. Narasimhadevara, Cancer Prevention Centre, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec, Canada; M. N. Pollak, Program in Cancer Prevention, McGill University, and Cancer Prevention Centre, Sir Mortimer B. Davis Jewish General Hospital; W. D. Foulkes, Program in Cancer Genetics, McGill University, and Cancer Prevention Centre, Sir Mortimer B. Davis Jewish General Hospital.

Correspondence to: William D. Foulkes, M.B. Ph.D., Cancer Prevention Centre – Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote Ste Catherine Road, Room C-107, Montreal, Quebec, Canada H3T 1E2 (e-mail: william.foulkes{at}mcgill.ca).

Veronesi et al. (1) report findings from the large-scale Italian Randomized Trial of Tamoxifen. Their results show that the risk-reducing effects of tamoxifen on high-risk women with breast cancer are most marked for estrogen receptor (ER)-positive tumors. Women at high risk were defined as being ER-positive tumors on the basis of a number of reproductive and hormonal criteria: height of greater than 160 cm, no oophorectomy, menarche by age 13 years, no full-term pregnancy before age 24 years. This group comprised 702 women (13.0%) of the total cohort (n = 5395). The results demonstrate that the criteria used to identify the high-risk cohort are valuable, especially in identifying women who may develop ER-positive tumors. These women are particularly suitable for enrollment into chemoprevention studies that interrupt estrogen pathways.

When comparing the results seen in the placebo group, high-risk women in the ER-positive group (cumulative incidence {approx}4.2% after 9 years, 11 events) showed an approximately 4.4-fold increased incidence of breast cancer over the low risk ER-positive group (cumulative incidence {approx}0.9%, 18 events). High-risk women in the ER-negative group (cumulative incidence {approx}1.1%, four events) showed only an approximately 2.2-fold increase over low-risk women (cumulative incidence {approx}0.5%, nine events).

The criteria were not designed to identify women at high risk of ER-negative breast cancer, and do not do so. Nevertheless, women who develop ER-negative breast cancers represent a very important group: these women have a worse prognosis than those who develop ER-positive cancers (2). In contrast to studies of ER-positive breast cancers (3), there are few epidemiologic studies that identify risk factors for ER-negative breast cancers. One study showed that family history was a strong risk factor for ER-negative status (4). Family history in this study may have been a surrogate for the presence of a BRCA1 mutation, because these women are more likely to develop ER-negative breast cancers than those who do not carry BRCA1 mutations (5). Another study showed that smokers and ex-smokers have a higher likelihood of ER-negative tumors than do never smokers (6). There is also evidence that African American women are more likely than white women to develop ER-negative tumors (7)—whether this reflects screening biases or true biologic factors is unclear.

Although these identified non-genetic risk factors appear to be very non-specific and the precise biologic mechanism associated with ER-negative status is not known, we would be interested in seeing whether Veronesi et al. (1) could use their large dataset to identify a population at high risk for ER-negative breast cancer. Proof that anthropometric, or other measured factors, can identify these women would be useful in helping to exclude women who are not suitable for interventions with selective estrogen receptor modulators, and would identify a cohort for consideration for preventive intervention with non-estrogen-related compounds.

REFERENCES

1 Veronesi U, Maisonneuve P, Rotmensz N, Costa A, Sacchini V, Travaglini R, et al. Italian randomized trial among women with hysterectomy: tamoxifen and hormone-dependent breast cancer in high-risk women. J Natl Cancer Inst 2003;95:160–5.[Abstract/Free Full Text]

2 Skoog L, Humla S, Axelsson M, Frost M, Norman A, Nordenskjold B, et al. Estrogen receptor levels and survival of breast cancer patients. A study on patients participating in randomized trials of adjuvant therapy. Acta Oncol 1987;26:95–100.[ISI][Medline]

3 Huang WY, Newman B, Millikan RC, Schell MJ, Hulka BS, Moorman PG. Hormone-related factors and risk of breast cancer in relation to estrogen receptor and progesterone receptor status. Am J Epidemiol 2000;151:703–14.[Abstract]

4 Krieger N, King WD, Rosenberg L, Clarke EA, Palmer JR, Shapiro S. Steroid receptor status and the epidemiology of breast cancer. Ann Epidemiol 1991;1:513–23.[Medline]

5 Chappuis PO, Nethercot V, Foulkes WD. Clinico-pathological characteristics of BRCA1and BRCA2-related breast cancer. Semin Surg Oncol 2000;18:287–95.[CrossRef][ISI][Medline]

6 Manjer J, Malina J, Berglund G, Bondeson L, Garne JP, Janzon L. Smoking associated with hormone receptor negative breast cancer. Int J Cancer 2001;91:580–4.[CrossRef][ISI][Medline]

7 Furberg H, Millikan R, Dressler L, Newman B, Geradts J. Tumor characteristics in African American and white women. Breast Cancer Res Treat 2001;68:33–43.[CrossRef][ISI][Medline]



             
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