Abstract
Breast cancer is a highly emotive and politically charged issue. The data suggest that one in every eight women will be affected during their lifetime. As detection and treatment have improved, more women will live through their disease and ultimately die from other causes.
Very recently, I have seen two women who are breast cancer survivors and who came to explore the options available to them for their menopausal symptoms. We followed the same assessment process and provided the same information to both. We sought a view from the same oncologist. Their ultimate decisions differed, but this should be seen as a strength, as they were supported to make a decision that was personal and appropriate.
The first lady we will call Trudy and is 53. She had found a lump in her right breast when she was 41 and her youngest child only 6. This was confirmed to be cancer, but the margins were not clear after lumpectomy, so she had a mastectomy. All nodes were clear, and it was deemed to be grade 1 ER+ (I did not know stage or PR status). To optimise benefit, she elected to have chemotherapy which lasted six months and then tamoxifen for five years. She had had six years without any treatment.
She had started to get menopausal symptoms with chemotherapy and they continued during and since the tamoxifen, though true periods did return for a couple of years after this was stopped. Twelve years on, she was fed up with their impact on her life.
The second (Judy) is now 55. She had found a lump near her nipple at the age of 39. She had no family history and was surprised when identified as having a grade 3 cancer. This was node negative. She had had two lumpectomies (as excision margins were not initially clear), five (of six) courses of chemotherapy, radiotherapy and then tamoxifen for five years. During this treatment, her periods never stopped and remained regular until just over two years ago. She has had menopause-related symptoms for the past four years, and they have become progressively worse and more intrusive and is now at the end of her tether.
Both women had been told that they could not consider HRT, and this remains a defined contraindication in product licenses.
The features common to risk assessment in these women were:
At 12 and 16 years, respectively, since their original diagnosis, recurrence risk from their original cancer can be reasonably expected to be very low. We cannot say that it does not exist, but it is implausible that metastasized breast cancer cells will have remained dormant for that length of time in women with menstrual cycles. A second primary is a more likely possibility, but there is nothing to suggest that this is greater than the population level risk. Other women are counselled regarding this risk but not denied HRT. One of these women had periods all through treatment and the other found they returned after treatment. Both will have already been exposed to fluctuating endogenous estrogen and progesterone at levels that are greater than we would expect from HRT. Neither had until this point considered this.
In many respects, the menopause consultation remained the same as always and considered the impact of symptoms, assessed gynaecological factors, bone risks without treatment and cardiovascular risks with and without. These women were, however, focussed on their breasts.
The mode of action and effectiveness of non-hormonal therapies needed to be explained. This included the herbal and prescribed options and their negative and positive effects. In women with hypertension, venlafaxine might not be a great idea. Any SNRI or SSRI will affect interest in sex and ability to achieve orgasm. This may not be a feature that a woman who already has relationship issues would want.
These two ladies were told that there are no trials of HRT in women in their situation, so long after diagnosis. There are trials in women with breast cancer which were started earlier after diagnosis, but all were stopped prematurely. Results are confusing, although it might be interpreted that those women taking HRT alongside tamoxifen saw little effect, while there was an increased recurrence risk in women taking aromatase inhibitors. One trial using Tibolone ran to five years before being stopped.1 This showed an overall 40% increase in recurrence but when stratified this was not significant in tamoxifen users. An increase of about 70% was seen in those women taking aromatase inhibitors. This needs to be explained clearly – a 40% increase in a number that is already small is a small absolute risk. It is not that 40% women will see a recurrence.
We then went through what we know of the actions of conventional combined estrogen and progestogen regimens and Tibolone on breast cancer risk in women who have not already had a cancer diagnosis. The NICE NG23 (Menopause) tables can be used to support this.2
We then look at what long-term data are available. There are few longer-term trials. The Danish osteoporosis prevention trial (ref) which lasted 16 years and the 18-year mortality date from the women’s health initiative (ref) do not show an increase in risk of dying and provide some context.
It is important to emphasise the limitations to our knowledge. However we should allow women to weigh this information for themselves and decide.
Both women were talked through the options should they decide to proceed with hormonal therapies.
Trudy went away with a prescription for Tibolone so that she could talk this all through with her husband. If she decided to go ahead, she was going to try 1.25 mg (half a tablet) daily. She later decided that she would see how the summer affected her and would do nothing for now. She was very clear, however, that she valued the two appointments it had taken her to make the decision and the opportunity to do so.
Judy decided that as she had had periods, she had already been exposed to estrogen and progesterone and had not apparently come to harm. She reasoned that if the combination of transdermal estrogen and micronised progesterone potentially offered her coronary artery protection with little impact on stroke or DVT risk she would opt for that as she had a strong family history. Given that sleep was a very major problem the sedative side-effect profile of micronised progesterone appealed to her. We started with a single measure of 0.06% estradiol gel (0.75 mg) with 100 mg micronised progesterone at night. I have yet to review but am confident that she has made the decision for herself.
I know a number of female colleagues who have opted to take HRT after a breast cancer diagnosis. It seems unfair to allow them to make a decision that is denied to others. The important features are that both a recurrence risk assessment and a discussion of the available evidence have occurred. The oncologist can help with the former and along with the menopause expert support the latter – this really should be a joint approach. This is a clear role for the specialist menopause clinic, and it is not something I would expect a GP to be able to do.