Re: Italian Randomized Trial Among Women With Hysterectomy: Tamoxifen and Hormone-Dependent Breast Cancer in High-Risk Women
Year: 2003
Type: letter
Abstract: 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 ≈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 ≈0.9%, 18 events). High-risk women in the ER-negative group (cumulative incidence ≈1.1%, four events) showed only an approximately 2.2-fold increase over low-risk women (cumulative incidence ≈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.
Institution: Jewish General Hospital
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2118941557