A new study examines the breast cancer risk for women who survived childhood cancer. Plus: Should doctors be more careful about using fluconazole during pregnancy? And, do elderly women derive benefit from breast cancer screening?
Female survivors of childhood sarcoma or leukemia who did not receive chest radiotherapy are at increased risk of developing breast cancer at a young age, according to a report from the Childhood Cancer Survivor Study. The risk, say the investigators, seems to be associated in a dose-dependent fashion with exposure to alkylators and anthracyclines and was not seen with any other primary cancer diagnosis.
Published in the Journal of Clinical Oncology, the findings are based on more than two decades of follow up on 3,768 female cancer survivors who had participated in the Childhood Cancer Survivor Study and had not been exposed to chest radiotherapy. Compared with the general population, the cancer survivors had a four-fold higher risk of developing breast cancer (standardized incidence ratio [SIR] = 4.0; 95% CI, 3.0 to 5.3], with the highest risk seen in women who had childhood sarcoma and leukemia.
The cumulative incidence of breast cancer by age 45 was 5.8% (95% CI, 3.7 to 8.4) in sarcoma survivors and 6.3% (95% CI, 3.0 to 11.3) in leukemia survivors. For both alkylators and anthracyclines, the P values for the dose-dependent increased risk were <.01.
With median follow up of 25.5 years (range, 8 to 39 years), 47 women developed breast cancer at a median age of 38.0 years (range, 22 to 47 years) and median of 24.0 years (range, 10 to 34 years) from primary cancer to breast cancer. The association between exposure to high-dose alkylator and anthracycline chemotherapy and risk of breast cancer, the investigators concluded, suggests a possible underlying gene-environment interaction that warrants further study.
Cohort study suggests caution in use of oral fluconazole in pregnancy
Results from a Danish study call into question the safety of prescribing oral fluconazole to pregnant women because of an association with an increased risk of spontaneous abortion. Their results, the investigators say, do not apply to use of the azole in topical form during gestation.
The findings are from a report on a nationwide register-based cohort study, published in JAMA. Data on more than 1.4 million fluconazole-exposed pregnancies in Denmark recorded between 1997 and 2013 were analyzed. The authors compared those pregnancies with up to four unexposed pregnancies matched for propensity score, maternal age, calendar year, and gestational age. (Gestational age was the first day of treatment and eligible controls survived through that date.)
Pregnancies during which the mothers were exposed to intravaginal topical azoles were used as an additional comparator group. The exposures were based on filled prescriptions for oral fluconazole obtained through the Danish National Prescription Register.
Of the 3315 women exposed to oral fluconazole during weeks 7 through 22 of their pregnancies, 147 (4.4%) had a spontaneous abortion, compared with 563 among the 13,246 (4.2%) matched women who had not been exposed to that drug formulation. Risk of spontaneous abortion was significantly increased in the women with the oral fluconazole exposure (HR, 1.48; 95% CI, 1.23-1.77). When exposures to topical and oral fluconazole were compared, the oral formulation also was associated with an increased risk of spontaneous abortion (HR, 1.62 [95% CI, 1.26-2.07]).
Looking at stillbirths, the investigators found no significant association between that outcome and exposures to oral fluconazole versus no exposure (HR, 1.32 [95% CI, 0.82-2.15]). The same was true for that outcome when comparing exposures to oral versus topical fluconazole during pregnancy (95% CI, 0.64-2.16).
While the authors concluded that caution may be advisable when considering use of oral fluconazole in pregnancy, they said any association between the drug formulation in pregnancy and stillbirth required further investigation. Our Editor-in-Chief points out that the actual rates of spontaneous abortion were extremely low in both exposed and unexposed cohorts, raising the issue of systematic bias.
Do elderly women benefit from annual mammograms?
An analysis of Medicare claims data suggests that as a group, black and white women older than age 74 may get some benefit, in terms of reduced breast cancer mortality, from annual mammographic screening. The finding runs contrary to recommendations from the American Cancer Society (ACS) and the United States Preventive Services Task Force (USPSTF) for case-by-case decisions about use of screening mammography in women aged 75 and older with a life expectancy of at least 10 years.
Results of the study of data from elderly women who lived in Surveillance, Epidemiology and End Results (SEER) geographic areas from 1995 to 2009, published in The American Journal of Medicine, showed lower 10-year breast cancer mortality in non-Hispanic women aged 69 to 84 at diagnosis who had annual mammograms than in a similar group who chose to have mammograms on a biennial basis or even less frequently. Among white women, hazard ratios for annual mammography were 0.31 (0.29-0.33) versus 0.47 (0.44-0.51) for biennial screening and, among black women, they were 0.36 (0.29-0.44) and 0.47 (0.37-0.58), respectively. The trends were similar overall and stratified by ages 69 to 74 years, 75 to 78 years, and 79 to 84 years and the researchers adjusted for stage at diagnosis, radiation therapy, chemotherapy, comorbid conditions, and contextual socioeconomic status. Risk of breast cancer mortality at 5 and 10 years after diagnosis was estimated using Cox proportional hazards regression.
The researchers also looked at potential harm from mammographic screening by calculating the percentage of women aged 65 to 84 during the period from 2002 to 2005 who had no or irregular biennial and annual testing and who had false-positive breast biopsies. They found that biennial screening would have resulted in 2.5% fewer biopsies among white women and 2.7% fewer biopsies among black women.
Beginning at age 55, the ACS recommends that women at average risk of breast cancer transition to biennial screening or have the opportunity to continue screening annually, with screening continuing as long as their overall health is good and they have a life expectancy of 10 years of more. The USPSTF recommends biennial screening mammography for women aged 50 to 74 who are not at high risk of breast cancer. Current evidence is insufficient, the organization says, on which to assess the balance of benefits and harms of screening mammography in women age 75 and older.
The authors did not include Hispanics because Hispanic whites have substantially lower mortality than non-Hispanic whites and the number of Hispanic blacks is small. White women in the current study who died of breast cancer, the researchers said, “tended to be older, to have a later stage at diagnosis, to have received chemotherapy, and to have a higher contextual socioeconomic status.” They were less likely to have undergone surgery or to have received radiation therapy.
In concluding, the authors said that they “believe the current evidence about potential benefits and harms from screening mammography in this population [women aged 65 to 84 years] is insufficient for policy decisions.” Their results “highlight the evidentiary limitations of data used for current mammography recommendations.”