The new review – which included data from 58 studies involving nearly 109 000 women from around the world – is the latest chapter in the ongoing story of these hormone therapies.
Marked decline in use
"Since the Women's Health Initiative [study] identified in 2002 that women who took hormone replacement therapy were at an increased risk for the development of breast cancer, we have seen a marked decline in their use," noted Dr Lauren Cassell, a breast surgeon at Lenox Hill Hospital in New York City. She wasn't involved in the new report.
"Patients who were on hormone replacement went off them [after the 2002 study], and physicians were more cautious in prescribing them," Cassell said.
The new report, published in The Lancet, "again reinforces that known increased risk, but more importantly, it identifies that the risk persists even after the therapy is stopped, and is affected by the length of time that the patient takes hormone replacement," Cassell said.
The new analysis was performed by a global team of experts known as the Collaborative Group on Hormonal Factors in Breast Cancer. They pored over data from 58 studies conducted worldwide between 1992 and 2018. These studies included nearly 109 000 women with breast cancer, with an average age of 65 at diagnosis.
Half of the women had received hormone therapy for menopause, the researchers noted. The average age at menopause was 50 and the average age at starting hormone therapy was also 50. Women took hormone therapy for an average of 10 years, in current users, and for seven years in past users, the team said.
For women of average weight living in Western countries who have never used hormone therapy, the average risk of developing breast cancer between ages 50 to 69 was about 6.3 per 100 women, according to the study.
However, the risk rose for women who received hormone therapy, and the formulation used seemed key to an uptick in risk.
For example, for women who took treatments involving oestrogen plus daily progestogen for five years, the rate of breast cancer was 8.3 per every 100 women. It was slightly lower for women taking oestrogen plus intermittent progestogen – 7.7 per 100.
The rate was lower – but still elevated – for women who used an oestrogen-only therapy: 6.8 cases per 100, the findings showed.
Duration of use mattered, as well. The rise in breast cancer risk was about twice as high for women who used hormone therapy for 10 years rather than five years, the study found.
Conversely, there was little increased risk of breast cancer after using any form of hormone therapy for less than a year, the researchers said.
One major finding was just how long hormone therapies left their mark for women who used the treatment for five years; any elevation in breast cancer risk didn't fully subside until 15 years after stopping the therapy.
Five years of use more likely
The findings suggest that all types of hormone therapy for menopause – with the exception of topical vaginal oestrogens – are associated with an increased risk of breast cancer, the study authors said.
"Our new findings indicate that some increased risk persists even after stopping use of menopausal hormone therapy," study co-author Valerie Beral, a professor at the University of Oxford in England, said in a journal news release.
The use of hormone therapy for menopause rose sharply in the 1990s, fell by half in the early 2000s and stabilised in the 2010s. Currently, there are about 12 million users in Western countries – about six million in North America and six million in Europe.
Ten years of use was once common, but about five years of use is now more likely, the researchers said.
Dr Alice Police directs breast surgery at Northwell Health Cancer Institute in Sleepy Hollow, New York. Looking over the study, she said that as time goes by, research like this is giving women better guidelines on what is or is not safe when it comes to hormonal therapies.
Progesterone use should be minimised
For example, "we now know that topical vaginal creams do not increase the risk of breast cancer as they mostly work locally and absorption is minimal. This is great news for many women who depend on these therapies to prevent UTIs [urinary tract infections] and vaginal dryness," Police said.
"We also know which medications, in what combinations, are the most dangerous," she added. "For example, oestrogen alone is safer than oestrogen and progesterone together."
For her part, Cassell said that, going forward, "oral hormone replacement therapy should be prescribed judiciously for patients who are having intolerable symptoms of menopause and understand the increased risk for breast cancer."
That means, "the use of progesterone should be minimised and the length of the hormone replacement should be as short as possible," Cassell said.
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