In the Journals

Breast cancer risk low in women with Turner’s syndrome

Women with Turner’s syndrome may be at an increased risk for various types of cancer, including bladder, melanoma and corpus uteri, but are at decreased risk for breast cancer.

Researchers at the U.K. Clinical Cytogenetics Group in Surrey, United Kingdom, developed a national cohort of 3,425 women diagnosed with Turner’s syndrome between 1959 and 2002. They followed the patients for cancer incidence for a mean 17 years per patient.

Not including non-melanoma skin cancer, researchers found 73 malignancies (standardized incidence ratio 0.9; 95% CI, 0.7-1.2). While the risk for breast cancer was lower in this population (n=10; SIR 0.3) than in the general population, women with Turner’s syndrome had an increased risk for central nervous system tumors, specifically meningioma (n=7; SIR 12.0) and childhood brain tumors (n=3; SIR 10.3). Risks were also higher in this population for cancers of the bladder, urethra and eye.

At ages 15 years to 44 years, the risk for corpus uteri cancer was higher (n=3; SIR 8.0). Gonadoblastoma of the ovary was reported during follow-up in five women with a Y-chromosome lineage. – by Stacey L. Adams

Lancet Oncol. 2008;doi:10.1016/S1470-2045(08)70033-0.

PERSPECTIVE

The most important thing to note about this epidemiological study is that overall cancers are not increased in Turner’s syndrome. Moreover, risk for breast cancer was actually significantly reduced among women with Turner’s syndrome compared to the general population. This is important since patients and caregivers worry about reports of possible breast cancer increase associated with hormone therapy for older women. This is the second epidemiological study reporting no increase in breast cancer in women with Turner’s syndrome. A small study was published in NEJM about a year ago that reported no increase in estrogen-treated Polish women with Turner’s syndrome, so this makes two studies with a fairly large number of women and years of observation for this rare population, which is reassuring.

This study did find an increase in brain tumors, mainly meningiomas. This reminds me of a study years ago that noted an increased prevalence of neuroblastoma in girls with Turner’s syndrome. These reports might suggest that practitioners need to be proactive in evaluating complaints of headache or neurological symptoms in patients with Turner’s syndrome.

It is interesting to note that there were only five gonadoblastoma diagnoses, all in individuals with Y chromosomes in their karyotype. Since there were 441 subjects with Y-positive karyotypes in the study, this represents a very low rate, in contrast to some estimates that have been as high as 10%. The major limitation of the study is the lack of clinical correlative information. For example, it is unknown if the gonadoblastomas presented clinically or, more likely, were found as a result of standard practice gonadectomy for girls with Y chromosome material. Nor do we know the prevalence of estrogen and progestin use among the women. If there were a large number of non-users, that would explain the reduced rate of breast cancer.

Carolyn Bondy, MD

Chief, Developmental Endocrinology Branch,
National Institute of Child Health and Human Development, NIH

Women with Turner’s syndrome may be at an increased risk for various types of cancer, including bladder, melanoma and corpus uteri, but are at decreased risk for breast cancer.

Researchers at the U.K. Clinical Cytogenetics Group in Surrey, United Kingdom, developed a national cohort of 3,425 women diagnosed with Turner’s syndrome between 1959 and 2002. They followed the patients for cancer incidence for a mean 17 years per patient.

Not including non-melanoma skin cancer, researchers found 73 malignancies (standardized incidence ratio 0.9; 95% CI, 0.7-1.2). While the risk for breast cancer was lower in this population (n=10; SIR 0.3) than in the general population, women with Turner’s syndrome had an increased risk for central nervous system tumors, specifically meningioma (n=7; SIR 12.0) and childhood brain tumors (n=3; SIR 10.3). Risks were also higher in this population for cancers of the bladder, urethra and eye.

At ages 15 years to 44 years, the risk for corpus uteri cancer was higher (n=3; SIR 8.0). Gonadoblastoma of the ovary was reported during follow-up in five women with a Y-chromosome lineage. – by Stacey L. Adams

Lancet Oncol. 2008;doi:10.1016/S1470-2045(08)70033-0.

PERSPECTIVE

The most important thing to note about this epidemiological study is that overall cancers are not increased in Turner’s syndrome. Moreover, risk for breast cancer was actually significantly reduced among women with Turner’s syndrome compared to the general population. This is important since patients and caregivers worry about reports of possible breast cancer increase associated with hormone therapy for older women. This is the second epidemiological study reporting no increase in breast cancer in women with Turner’s syndrome. A small study was published in NEJM about a year ago that reported no increase in estrogen-treated Polish women with Turner’s syndrome, so this makes two studies with a fairly large number of women and years of observation for this rare population, which is reassuring.

This study did find an increase in brain tumors, mainly meningiomas. This reminds me of a study years ago that noted an increased prevalence of neuroblastoma in girls with Turner’s syndrome. These reports might suggest that practitioners need to be proactive in evaluating complaints of headache or neurological symptoms in patients with Turner’s syndrome.

It is interesting to note that there were only five gonadoblastoma diagnoses, all in individuals with Y chromosomes in their karyotype. Since there were 441 subjects with Y-positive karyotypes in the study, this represents a very low rate, in contrast to some estimates that have been as high as 10%. The major limitation of the study is the lack of clinical correlative information. For example, it is unknown if the gonadoblastomas presented clinically or, more likely, were found as a result of standard practice gonadectomy for girls with Y chromosome material. Nor do we know the prevalence of estrogen and progestin use among the women. If there were a large number of non-users, that would explain the reduced rate of breast cancer.

Carolyn Bondy, MD

Chief, Developmental Endocrinology Branch,
National Institute of Child Health and Human Development, NIH