OESTROGEN and BREAST CANCER

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> Warning of risk to breast cancer patients from vaginal oestrogen

> http://www.eurekalert.org/pub_releases/2006-01/esfm-wor012306.php

> Research shows it may stop new breast cancer drugs working say UK

> specialists

>

> Breast cancer specialists from one of the UK's leading cancer centres

> cautioned doctors (Thursday 26 January) of the risks in prescribing vaginal

> oestrogen to breast cancer patients being treated with the new aromatase

inhibiting

> drugs, anastrozole, letrozole and exemestane[1].

>

> Their concerns follow findings from the first study to examine the impact of

> vaginal oestrogen in women receiving aromatase inhibitors (AIs) for breast

> cancer, published on-line today in ls of Oncology[2], by a team from the

> Royal Marsden NHS Foundation Trust in London.

>

> AIs work by inhibiting the enzyme aromatase, which promotes the conversion

> of androgens to oestrogens in postmenopausal women. Breast cancer feeds off

> oestrogen, so reducing the circulating levels of the hormone as much as

> possible lessens the chance of the cancer recurring. The new AIs reduce

circulating

> oestradiol by over 97%.

>

> Around a fifth of patients on adjuvant AIs suffer from atrophic vaginitis –

> a distressing skin condition of the genitals caused by lack of oestrogen.

> Many ask if they can use topical oestrogen to alleviate the symptoms as

> conventional HRT is not recommended.

>

> Senior author Professor Ian , Head of the Breast Unit at the Royal

> Marsden, said: " Using this vaginal form of oestrogen which, we found,

increases

> systemic oestradiol levels, will counteract AI treatment. With long term use,

> women may be risking the chance that their cancer may return, although this

> is probably not an issue if oestrogen rises for only one to two months. "

>

> Using a sensitive radioimmunoassay that they developed to quantify even

> extremely low levels, the researchers measured serum oestradiol[3] in six

women

> on adjuvant AI therapy who had actively asked to use the vaginal oestradiol

> tablet Vagifem for severe symptoms of atrophic vaginitis. They also monitored

a

> seventh patient with metastatic breast cancer who was using Premarin

> oestradiol cream. Measurements were taken at baseline, then at 2, 4, 7-10

weeks and

> over 12 weeks from starting Vagifem.

>

> Lead Researcher Dr Anne Kendall, Clinical Research Fellow at the Academic

> Department of Biochemistry at the Royal Marsden, said: " Our results showed a

> significant rise in serum oestradiol levels two weeks after starting Vagifem

in

> six of the seven women (five of those on Vagifem and the one on Premarin).

> Typically, they fell after one month, but with a return to pre-Vagifem levels

> in only two women after seven and 12 weeks respectively. Two women who

> continued using Vagifem showed further increases between weeks seven and 10. "

>

> Dr Kendall said that in the UK and the USA there was currently uncertainty

> among cancer specialists and other doctors, including gynaecologists, about

> the safety of preparations such as Vagifem for women receiving AIs, and they

> are widely used. Some doctors do measure serum oestradiol, but most assays are

> not sensitive enough to detect changes in the low levels seen in women on

> AIs.

>

> Although Vagifem is supposed to be used for a maximum of three months at a

> time, recurrence of symptoms often means repeat courses are prescribed. The

> manufacturers' [4] patient information sheet does state that Vagifem should

not

> be used in women with a history of breast cancer, but it also states that

> although there are reports of increased risk of breast cancer in women on HRT,

> Vagifem is not expected to pose an increased risk.

>

> Professor said: " Although the study is small, the magnitude of the

> effect in such a high proportion of the women strongly indicates it would be

> reproduced in a larger study population. It is particularly important that

> doctors are aware of the new findings, as increasing uptake of AI therapy

means

> that it is likely that around 15,000 new women a year in the UK would be

> receiving AIs, a total of 100,000 at any one time. "

>

> The women in the study had been warned at the outset that they would be

> recommended to stop using the topical preparation at an early stage if there

were

> concerns. One patient continued to use a low dose with regular monitoring.

> One elected to stop AI treatment and continue with Vagifem because of her poor

> quality of life. The others have stopped.

>

> Dr Kendall said: " Our results raise concerns over the appropriateness of the

> combination of AI treatment and Vagifem, since the efficacy of aromatase

> inhibition depends on near total suppression of oestrogenic stimulation. The

> third generation AIs that inhibit aromatase by over 97% are more effective in

> controlling breast cancer than earlier agents, which achieved only 90%; this

> suggests that even a small increase in systemic oestrogen may be detrimental. "

>

> She added: " Our view is that the combination of AIs and Vagifem is

> contraindicated, apart from exceptional circumstances where regular monitoring

of

> plasma oestradiol with specialist assays is available. Other non-hormonal

vaginal

> moisturising gels or creams should be used in most cases. " She said it was

> impossible to generalise about all vaginal oestrogens. However, given that a

> similar effect was seen with Premarin cream, caution was needed with all

> topical oestrogens.

>

> Professor concluded: " It is important that women discuss this with

> their doctor. Some complications related to atrophic vaginitis, such as

> recurrent urinary tract infection, may need treatment to be completed before

stopping

> Vagifem. One option in those cases would be to switch from AIs to tamoxifen,

> which appears not to allow as much oestrogen to enter the system. "

>

> ###

> [1] Anastrozole (Arimidex); Letrozole (Femara); Exemestane (Aromasin)

>

> [2] Caution: Vaginal estradiol appears to be contraindicated in

> postmenopausal women on adjuvant aromatase inhibitors. ls of Oncology.

> doi:10.1093/annonc/mdj127.

>

> [3] The baseline oestradiol serum levels for all the women (except the one

> on exemestane, a drug that can interfere with the assay used to measure

> oestradiol) were under or around 5pmol/l [picomoles per litre]. By 14 days

they had

> risen from a median of 3 to 72pmol/l (range 3-232 pmol/l). By 28 days there

> was a drop in the majority to less than 35 pmol/l, but in two women who

> continued on Vagifem there was a further increase to 219 and 137 pmol/l

> respectively between 7 and 10 weeks.

>

> [4] Vagifem is manufactured by Novo Nordisk. It comes in the form of a

> tablet that is inserted in the vagina via an applicator.

>

> ls of Oncology website: http://annonc.oxfordjournals.org/

>

>