Women on HRT more likely to develop advanced breast cancers

By Lilian Anekwe

Older women who are prescribed combined HRT are more likely to develop advanced forms of breast cancer, according to the latest data from the Women's Health Initiative (WHI).

The study analysed 11 years of follow-up data and found the combined use of oestrogen and progestin increased the incidence of advanced breast cancers, with a higher number of deaths attributable to breast cancer.

The original WHI study, published in 2002, showed breast cancer incidence was increased among women who received combined HRT compared to placebo but this is the first data on breast cancer mortality.

A total of 16,608 postmenopausal women aged 50 to 79 years with no prior hysterectomy were randomly given either combined 0.625mg/d oestrogen and 2.5mg/d progesterone, or a placebo pill.

Combined HRT was associated with a 25% increased risk of more invasive breast cancers compared with placebo.

Breast cancers in the group given combined HRT were similar in histology and grade to breast cancers in the placebo group but were more likely to be node-positive, where cancerous cells have spread to the lymph nodes, meaning there is a higher chance of the cancer returning and spreading.

There were more deaths directly attributed to breast cancer (25) in the HRT group than the 12 deaths recorded in the group given a placebo, and there were more deaths from all causes occurring after a breast cancer diagnoses recorded in the HRT than the placebo group, at 51 and 31, respectively, though the differences in breast cancer and all-cause deaths did not reach statistical significance.

Professor Rowan Chlebowski, professor of medicine at the University College of Los Angeles concluded: ‘Oestrogen plus progestin was associated with greater breast cancer incidence, and the cancers are more commonly node-positive. Breast cancer mortality also appears to be increased with combined use of oestrogen and progestin.

‘In the WHI trial, combined hormone therapy increased breast cancer risk and interfered with breast cancer detection, leading to cancers being diagnosed at more advanced stages.

‘Now, with longer follow-up results available, there remains a cumulative, statistically significant increase in breast cancers in the combined hormone therapy group, and the cancers more commonly had lymph node involvement. The observed adverse influence in breast cancer mortality of combined hormone therapy can reasonably be explained by the influence on breast cancer incidence and stage.'

In an accompanying editorial, Dr Peter Bach, associate attending physician at Memorial Sloan-Kettering cancer center in New York, wrote: ‘Clinicians who prescribe brief courses of hormone therapy for relief of menopausal symptoms should be aware that this approach has not been proven in rigorous clinical trials and that the downstream negative consequences for their patients are of uncertain magnitude.

‘One option – discussing with patients the risk-benefit trade-offs may seem to be a reasonable approach. But informed patients decisions are not valid when the information underlying the decision is itself speculative.'

Dr Sarah Gray, a council member of the British Menopause Society and a GP in Truro, Cornwall, said: ‘The key is that GPs prescribe HRT to women on an individual basis and not make generalisations. There are problems with the WHI study, as the women were much older than we usually prescribe to, and women in the US have a higher average BMI which may put them at higher risk of breast cancer. GPs should initiate HRT at the lowest effective dose, and for the shortest possible time, for symptom relief.'

JAMA. 2010;304(15):1684-1692.

Oestrogen-progestin versus placebo among healthy postmenopausal women found that, compared with placebo, women receiving oestrogen plus progestin experienced:

• increased risk of myocardial infarction
• increased risk of stroke
• increased risk of blood clots, including deep venous thrombosis and pulmonary embolism
• increased risk of breast cancer
• decreased risk of colorectal cancer
• fewer fractures

Source: US National Health Lung and Blood Institute