eMJA: Safety of hormone replacement therapy after mastectomy

Letters

Safety of hormone replacement therapy after mastectomy

Robert N Hitchins

MJA2002; 176 (12): 617-620

To the Editor: I agree with the assessment by Del Mar and colleagues of available data according to evidence-based guidelines on hormone replacement therapy (HRT) after mastectomy.1 As they note, these data are not definitive. Standard practice has been to avoid oestrogen use in women with a history of breast cancer.

Ours is an increasingly litigious society and courts make decisions according to different criteria than do scientists. In particular, precedent is very important to the law of tort, even if the scientific basis for the precedent is unproven.

For some years now, I have seen 100 or more new patients per year with recently diagnosed early breast carcinoma. By the time I see them, every single one already knows that:

anti-oestrogens are used in treatment of breast cancer; and
women are at least 30% more likely to develop breast cancer after five years of HRT.

Further, these women fear recurrence of breast cancer more than any other health problem.

Hence, I am concerned that the sound evidence-based conclusions reached by Del Mar and colleagues could be successfully challenged in court by a woman who developed recurrence of breast cancer while receiving HRT.

In addition to the costs and stress for the individual practitioner involved and other members of his medical indemnity organisation, such action would set back scientific enquiry into this important subject, possibly forever.

There is a wealth of well conducted research into non-oestrogenic management for menopausal symptoms. Lifestyle measures (clothing and activity) and dietary modifications (avoiding spicy foods, alcohol) have a role in well-being. Oral progestogens, clonidine, venlafaxine, black cohosh, and probably tibilone, all produce better outcomes than placebo.2 Evening primrose oil, pyridoxine, dong quai, Chinese herbs, progestogen and yam creams, and phytoestrogens do not work better than placebo.3 The last may actually be harmful. Advisory statements for general practitioners about oestrogen replacement therapy for managing menopausal symptoms after breast cancer should be prefaced with this information, as should any discussion with patients. I do prescribe oestrogens for distressing menopausal symptoms after breast cancer treatment, but only after several consultations to allow time for women to appreciate the uncertainties involved.

Del Mar CB, Glasziou PP, Spinks AB. Safety of hormone replacement therapy after mastectomy. Med J Aust 2002; 176: 285. <PubMed>
Davis SR. Menopausal symptoms after breast cancer. Australian Doctor 2002, 1 February.
Eden J. Managing menopause after breast cancer. Proceedings of Annual Hormone Update and Education Day, Sydney: Sydney Menopause Centre, 16 February 2002.

(Received 28 Mar 2002, accepted 9 May 2002)

Allamanda Medical Centre, Southport, QLD.

Robert N Hitchins, MB BS, FRACP, FAChPM, Medical Oncologist and Palliative Care Physician.

Correspondence: Dr Robert N Hitchins, Allamanda Medical Centre, 25 Spendelove Avenue, Southport, QLD 4215. hmedplATozemail.com.au

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John A Eden

To the Editor: I was pleased to see the issue of hormone replacement therapy (HRT) after breast cancer raised by Del Mar and colleagues in a recent issue of the Journal.1 However, I was a little disappointed to see that Australian research in this area had been "missed" by their search.2,3 There are a number of other studies that I am aware of which would suggest to me that perhaps their search technique was not particularly thorough.4-7

Nonetheless, I should add that I do agree with their conclusions. In fact, I am not aware of any clinical trials that have shown an adverse effect of HRT after a diagnosis of breast cancer. However, the studies examined by Del Mar and colleagues are all population studies and not randomised controlled trials.

I also think it's important that the readers of the Journal understand that there are other strategies for controlling menopause symptoms after breast cancer, such as the use of progestins, antidepressants and stress-reduction techniques. Even though the evidence we have suggests that HRT after breast cancer is "safe", we do not have even one published randomised trial on this question, so caution should be the rule. HRT after breast cancer should always be viewed as a last resort.

Del Mar CB, Glasziou PP, Spinks AB. Safety of hormone replacement therapy after mastectomy. Med J Aust 2002; 176: 285. <PubMed>
Eden JA, Bush T, Bush N, et al. A case controlled study of combined continuous estrogen-progestin replacement therapy among women with a personal history of breast cancer. J Nth Am Menopause Soc 1995; 2: 67-72.
Dew J, Eden J, Beller E, et al. A cohort study of hormone replacement therapy given to women previously treated for breast cancer. Climacteric 1998; 1: 137-142. <PubMed>
Stoll BA, Parbhoo S. Treatment of menopausal symptoms in breast cancer patients. Eur J Cancer Clin Oncol 1989; 25: 1909-1913. <PubMed>
Vassilopoulou-Sellin R, Asmar L, Hortobagyi GN, et al. Estrogen replacement therapy after localized breast cancer: clinical outcome of 319 women followed prospectively. J Clin Oncol 1999; 17: 1482-1487. <PubMed>
Brewster WR, DiSaia PJ, Grosen EA, et al. An experience with estrogen replacement therapy in breast cancer survivors. Int J Fertil Womens Med 1999; 44: 186-192. <PubMed>
Puthgraman K, Natrajan MD, Soumakis K, Gambrell RD. Estrogen replacement therapy in women with previous breast cancer. Am J Obstet Gynecol 1999; 181: 288-295. <PubMed>

(Received 4 Apr 2002, accepted 9 May 2002)

School of Women's & Children's Health, Royal Hospital for Women, Randwick, NSW.

John A Eden, MB BS, MD, FRACOG, FRCOG, MRCOG, CREI, Associate Professor Reproductive Endocrinology, University of New South Wales, and Director, Sydney Menopausal Unit.

Correspondence: Professor John A Eden, School of Women's & Children's Health, Royal Hospital for Women, Locked Bag 2000, Randwick, NSW 2031. j.edenATunsw.edu.au

To the Editor: While I have little concern with the conclusion of the article by Del Mar and colleagues,1 I have some concerns about its use to portray a mode of healthcare delivery where any given health practitioner, armed only with what can be gleaned from the Internet, can issue advice.

For example, in such a circumstance, should not the general practitioner also refer to the National Health and Medical Research Council clinical practice guidelines on the management of early breast cancer,2 which suggests that the "safety of oestrogen replacement therapy in women with breast cancer has not yet been established", and, further, that "HRT [hormone replacement therapy] and women with breast cancer" is an area where research is needed?

Should the doctor also point out to the patient that she is eligible to enter a prospective randomised trial looking at the use of HRT following breast cancer treatment versus the best non-hormonal treatment of menopausal symptoms, currently being administered by the Australian and New Zealand Breast Cancer Trials Group (as part of International Breast Cancer Study Group trial 17-98)?

How should practitioners protect themselves when they find the management they are recommending is outside that recommended in the evidence-based guidelines published by specialty groups?

A few other minor points: the content of the article refers to women with breast cancer, whereas the title refers only to women who have had mastectomy, and the imaginary patient asked about loss of libido, which was not addressed at any subsequent point in the article.

In reply: Eden, Pyke and Hitchins are happy with the findings of the rapid literature search that we performed for the general practitioner who wanted to know about the safety of HRT in a woman treated for breast cancer. However, they have concerns with the process. Eden is worried that we missed two Australian publications on the issue.

In fact, they misunderstand our intentions. Firstly, we did not raise the issue, nor deliver an "advisory statement". It was the general practitioner who asked the question. We were trying to provide a rapid (few days) and responsive service to provide credible information to help a doctor manage a patient. Secondly, we were not able to undertake a full systematic review (which would take a full-time researcher as long as six months and would cost accordingly).1 Instead, our best strategy was to use a cascade process of searching, looking first for the most rigorous study types that would answer the clinical question. If not available we go to the next most rigorous, and so on, stopping when we find the relevant evidence.2 For this question, the ideal study type would be a meta-analysis of randomised controlled trials (RCTs). However, no RCTs were available (as Eden, and the guidelines to which Pyke refers, note), and we had to content ourselves with observational studies. We should remember that no evidence for safety is not the same as evidence for danger. What is important is that we did not miss any trials.

Legal issues worry many doctors, even when decisions are supported by best research evidence,3 but, rather than pose a medicolegal threat, we believe that this evidence-based approach is more likely to protect doctors. Why? Failures in communication are the most common preventable cause for doctors being sued by patients.4 Yet, taking the trouble to find empirical information such as this and then discussing it with the patient is surely the most effective way of communicating the pros and cons of different treatment strategies (including, we agree, alternatives such as those mentioned by Hitchins). In the end the patient has to decide on the basis of the risks and benefits, and the choice can often be extremely difficult. It is likely to be more dangerous to assume the patient has abdicated this responsibility to the doctor without checking first. Can doctors be sued for a "safe" decision that leaves a patient exposed to unnecessary symptoms? It may be dangerous to assume that doctors can play "safe" in any one direction.

Why do experts take exception when non-experts delve in their areas for the best evidence to manage patients? After all, a cat may look at a king.5 Experts seem to welcome the attention, but seem to think they should be dispensing the information. However, until the information can be delivered more effectively, this sort of stopgap system will have to do.