24 August, 2015

Breast cancer can occur in women below 50 years old and represents 25% of the total number of cases. Risk factors and histological characteristics of breast cancer are different in young women compared with older women. There are many publications on the risk of breast cancer and hormone treatment (MHT) in postmenopausal women. However, less is known about use of MHT in young women and especially looking separately at the impact of estrogen-only treatment (ET) and combined estrogen–progestin treatment (EPT). A recent study aimed to investigate whether the use of MHT is a risk factor for young-onset breast cancer [1]. The authors used the Two Sister Study for this purpose. It is a sister-matched case–control study of young-onset breast cancer from the Sister Study, a prospective cohort study of 50,884 women without breast cancer who had a full or half sister who had been diagnosed with breast cancer; 1422 cases and 1689 controls were included. Because 10% of control sisters and no case sisters had reached the age of 50 years before 2002 when the WHI study was published and because MHT prescriptions decreased drastically thereafter, a propensity score was used to decrease the impact of this bias. Results show that a low percentage of women used MHT. The most frequent was ET (7% of controls and 4% of cases), then EPT (3% and 2%, respectively) and progestin alone (PT) (1% and 1%). Crude odds ratios (OR) for breast cancer were less than 1 for every MHT category except PT. ET use was inversely associated with young-onset breast cancer (propensity score, adjusted OR =0.58; 95% CI 0.34–0.99); the adjusted OR for EPT use was 0.80 (95% CI 0.41–1.59) and for PT was 1.51 (95% CI 0.76–3.00). Adjustment for duration of use, age at first use, menopausal status at first use, and recency of use did not appear to modify the association. There was no interaction by oophorectomy status but women using ET were more often hysterectomized and oophorectomized. The authors concluded that neither ET nor EPT increase the risk of young-onset breast cancer and that ET might be associated with a reduced risk.

Comment

This study suggests that ET is associated with a decrease in the risk of breast cancer, as in the WHI randomized, controlled trial; the results also suggest that EPT does not increase the risk in young women.

The design of this study is original. It consists of a case–control study among a cohort of sisters with and without breast cancer. One of the biases is due to the different ages of the sisters. As a consequence, a possible birth cohort effect for frequency of MHT use can be operating. Methods are used to decrease this bias. In this study, however, the indication of 'hormonal treatment' was not fully clear. It was prescribed for surgical menopause, but also in perimenopausal or premenopausal women; this raises questions about the heterogeneity of the indications and thus of treated women. Furthermore, the number of women treated was rather low. Nevertheless, this study fits quite well with a previously published paper from a large database for breast cancer, the Breast Cancer Surveillance Consortium (a national collaboration of five mammography registries and two affiliate sites in the US) which reported a reduced risk for breast cancer compared to non-users in young women with no uterus currently using menopausal hormone therapy (RR 0.70; 95% CI 0.52–0.95) [2]. The reduced risk is likely to be associated with ET since it occurs in hysterectomized women. Similarly, in the DOBS, a randomized trial between MHT and no treatment, women younger than 50 years old had a significantly reduced risk of mortality (composite score) or breast cancer (RR = 0.49; 95% CI 0.28–0.87; p = 0.015) [3]. MHT is recommended in women less than 50 years with premature ovarian insufficiency because of its benefits for quality of life and cardiovascular protection. There are now several studies showing that it can be associated with a decrease or no increase in the risk of breast cancer as well, which is an important observation.

Anne Gompel
Unité de Gynécologie Endocrinienne, Université Paris Descartes, APHP, Cochin Port Royal, Paris, France

References

1. O'Brien KM, Fei C, Sandler DP, et al. Hormone therapy and young-onset breast cancer. Am J Epidemiol 2015;181:799-807
http://www.ncbi.nlm.nih.gov/pubmed/25698646 
2. Nelson HD, Zakher B, Cantor A, et al. Risk factors for breast cancer for women aged 40 to 49 years: a systematic review and meta-analysis. Ann Intern Med 2012;156:635–48
http://www.ncbi.nlm.nih.gov/pubmed/22547473 
3. Schierbeck LL, Rejnmark L, Tofteng CL, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ 20129;345:e6409 
http://www.ncbi.nlm.nih.gov/pubmed/23048011