Ovarian ablation for early breast cancer

Reason for withdrawal from publication

The most up‐to‐date results from the EBCTCG overview are available from the Clinical Trial Service Unit and Epidemiological Studies Unit website (http://www.ctsu.ox.ac.uk/projects/ebctcg/) and reprints of the EBCTCG papers can be requested by emailing bc.overview@ctsu.ox.ac.uk

The Early Breast Cancer Trialists Collaborative Group (EBCTCG) conducts periodically updated individual patient data meta‐analyses of randomised trials pertaining to the effects of local and systemic therapy on recurrence, second cancers and mortality. These systematic reviews are of the highest quality, are updated every five years and are published in prominent peer‐reviewed journals. They represent the best available evidence on the effects of these treatments on relapse, second cancer and death.  

Converting each of the EBCTCG reviews into a Cochrane format as they are updated represents unnecessary duplication of effort and this Cochrane review, which was based on earlier cycles of data collection and analysis by the EBCTCG, has now been withdrawn.

The editorial group responsible for this previously published document have withdrawn it from publication.

Feedback

Ovarian ablation for early breast cancer

Summary

Comment submitted by Heather Goodare

Implications for Practice

With survival benefit for ovarian ablation estimated at approximately six percent at 15 years, women will want to know to what extent their quality of life will be affected if they except this treatment. Younger women thrust into a sudden early menopause need to come to terms with their loss of fertility and the accompanying disorders of the climacteric. These 'side effects' are not merely 'possible': most are inevitable. As well as hot flushes and sweats, weight gain, vaginal dryness and resulting dyspareunia, bone mineral loss (sometimes resulting in severe joint pain) and greater risk of osteoporosis and heart disease, the psychosocial effects must not be underestimated. Mood swings and insomnia are common, and depression may well result, especially if these issues have not been thoroughly worked through before treatment. Sexual intimacy is bound to be affected and partners need to be involved in discussions.

The different long‐term side‐effects of ovarian ablation by surgery, irradiation or chemotherapy (see implications for research) need to be weighed up in discussions with women, giving them the opportunity to choose whichever method agrees best with their lifestyle choices. Since for women with breast cancer going through an artificial menopause hormone replacement therapy is contrary‐indicated, alternative treatments need to be considered.

Common side effects of ovarian ablation are well known. But some of the less well‐known effects need to be considered in certain circumstances. The great contralto singer Kathleen Ferrier, with already advanced breast cancer, refused an oophorectomy in 1953 after consulting with her laryngologist, James Ivor Griffiths, who said 'I told her that the long term effects on the cancer would be negligible but the long‐term effect on her voice might be disastrous.' (1)

Implications for Research

In this overview, individual patient data for ovarian ablation by means of surgery or irradiation were obtained for 12 studies, but not for the four studies using chemotherapy. Further research should assess to what extent the long‐term side effects of the first two methods are different, and which method is found more acceptable to women. Both methods also need to be compared to ovarian suppression by chemotherapy, again with quality of life assessed as well as survival. As Susan Love remarks, 'These forms of menopause have not been well studied.' (2) Tamoxifen may also bring about an early menopause, depending on how near to the normal menopause a woman is already.

It is time that breast‐cancer trials differentiated more precisely between pre‐‐ and postmenopausal women. Modern technology can evaluate the hormonal status of the woman: the timing of the natural menopause is variable, and there is no longer any reason for using age as the reference.

Also, if tumors were properly evaluated the success of treatment would surely be greater than the extremely modest figure of 6% than in. An urgent requirement in all research on andadjuvant treatments for breast cancer is to include in the data hormone receptor assays, which are still not done routinely in some hospitals.

So, a new research question might be: 
 Q. How may patients be selected for hormone manipulations who are most likely to benefit enough to justify the side‐effects?

(1) Leonard M Kathleetn: The life of Kathleen Ferrier 1912‐1953. 
 London, Futura, 1998

(2) Love S Dr. Susan Love's Hormone Book New York, Randon House, 1997.

Heather Goodare on behalf of BREAST UK (Breast cancer Research Ethics, Advocacy Strategy)1 Heron Way, Horsham, West Sussex RH13 6DF, UK. Tel. 01403 261674

I certify that I have no affiliations with or involvement in any organisation or entity with a direct financial interest in the subject matter of my criticisms.

Reply

The Early Breast Cancer Trialists' Collaborative Group review of the individual patient data from randomised trials provides the most reliable evidence available on the effects of ovarian ablation on breast cancer recurrence and survival. It shows a clear, moderate, but important improvement in both these outcomes for at least the first 15 years after treatment. However, the review is unable to provide evidence on the effects of the treatment on other, non‐fatal outcomes, due to resource constraints on a project of this scale and difficulties in collecting and combining data for many of these outcomes.

The evidence from this review is that there is little, if any, difference in the effect on recurrence and survival from ovarian ablation by radiotherapy compared to ovarian ablation by surgery. This is based on an indirect non‐randomised comparison of the two forms of treatment. The Early Breast Cancer Trialists' Collaborative Group have been able to identify almost no direct randomised evidence comparing ovarian ablation by radiotherapy with ovarian ablation by surgery in women with early breast cancer. The next cycle of the review will include data from the trials of ovarian suppression by drugs. It is hoped that these results will be available for publication in 2002. The trials of ovarian suppression by drugs were too immature at the time of the data collection for the review reported here to be included.

Although future randomised trials might be better able to clearly distinguish between pre‐ and post‐menopausal women, it will never be possible to obtain menopausal status information more reliably for the women in the trials in this review. Therefore, this review needs to continue to use the age of 50 years at randomisation as an indicator of menopausal status.

If reliable information on the hormone receptor status of a woman's tumour is available in the data collected from randomised trials, subgroup analyses will be performed for the review on the basis of this variable.

Contributors

Mike Clarke (contact for EBCTCG) 
 John Simes (comments and criticisms editor)

What's new

Date	Event	Description
6 August 2008	Amended	Converted to new review format.

History

Protocol first published: Issue 1, 1998
 Review first published: Issue 2, 1998

Date	Event	Description
16 January 1998	New citation required and conclusions have changed	Substantive amendment

Sources of support

Internal sources

• No sources of support supplied

External sources

• Cancer Research UK (formerly Imperial Cancer Research Fund UK), UK.

Withdrawn from publication for reasons stated in the review