ECC 2015

Hormonal suppression prevents ovarian failure, preserves fertility in women with breast cancer

Dr Matteo Lambertini - Ospedale San Martino, Genoa, Italy

Matteo, thanks for coming here in Vienna. You’re from Italy, you’ve been looking at avoiding premature ovarian failure. Tell me about your centre and what your position is in that centre.

Yes, I’m still a Fellow in Medical Oncology, I’m completing my residency, I have just a few months left. I work with Dr Del Mastro in the Department of Medical Oncology at the San Martino, it’s in Genoa, Italy.

Why were you so interested in looking at breast cancer therapy for younger patients and the difficulties it makes for them if they want to have a baby?

Because breast cancer in young women occurs in approximately 11% of all cancer diagnoses every year and one of the side effects of chemotherapy in these young patients is the possible occurrence of premature ovarian failure and subsequent infertility. A lot of these patients still desire to have a pregnancy after cancer treatment and so this is a very important topic.

So what did you do in the study?

We performed a meta-analysis of randomised studies to evaluate the role of temporary ovarian suppression with a hormonal agent called an LHRH analogue administered during chemotherapy as a strategy to preserve ovarian function and fertility in young breast cancer patients.

There are alternatives if you want to have babies, though, aren’t there?

Yes, the standard strategies to date for fertility preservation in cancer patients are cryopreservation of embryos or oocytes, these are the standard strategies, but these strategies can preserve fertility, so the possibility to have babies in the future, but not the overall ovarian function. So patients might be still at risk of developing early menopause.

So what are the benefits potentially of using temporary ovarian suppression rather than going for cryopreservation and just going ahead with your chemo?

The major advantage is that the LHRH analogue can preserve not only fertility, so the possibility  to have babies in the future, but mainly ovarian function, so trying to avoid the risk of going into menopause early, in early menopause.

What did you find?

We found that the use of an LHRH analogue was associated with a statistical reduction in the risk of developing premature ovarian failure, defined in each eligible study, but also we found that the use of an LHRH analogue reduced statistically significantly the number of patients developing one year amenorrhoea. Also we found a higher number of patients achieving pregnancy after treatment with the use of this strategy as compared to those who received chemotherapy alone.

And the numbers are quite impressive, aren’t they? I seem to remember you halved the incidence of premature ovarian failure.

Yes, we found a weighted hazard ratio of 0.36, that means a 64% reduction in the risk of developing this side effect.

And to prove a point, some of your women got pregnant.

Yes, 33 patients across all the studies in the LHRH analogue arm achieved pregnancy as compared to 19 in the control arm, so in patients receiving chemotherapy alone.

Now is there a downside to using LHRH agonists as therapy?

The LHRH agonists, their action is to make a kind of pharmacological menopause and so patients might suffer some side effects of menopause such as hot flushes or sexual dysfunction. However, the use of this strategy is just for the 5-6 months of chemotherapy so this might not impact too much on the quality of life of these patients. Only two trials reported adverse events with the LHRH analogue in these studies and they did not find any significant difference in side effects between patients enrolled in the chemotherapy alone arm as compared to those in the LHRH analogue arms.

Of course, if you use temporary ovarian suppression you don’t have to delay your chemotherapy.

No, that’s true. This strategy can be started just the day before the initiation of chemotherapy and then administered for all the duration of treatment.

So what are your recommendations to doctors who might be advising young women patients about their treatment for breast cancer, many of whom, I gather, as many as half, still want to have a baby?

For patients who are really interested in preserving their fertility, embryo and oocyte cryopreservation are still the standard strategies for fertility preservation and the strategy with the most reliable results. However, in these patients and also in those who are interested in maintaining ovarian function more than fertility, who are afraid of developing early menopause and they need to have a baby in the future, for these patients the use of an LHRH analogue might be considered a valid option to preserve their ovarian function and might be used also in patients who underwent prior oocyte or embryo cryopreservation to improve their chances to have babies in the future.

So could you summarise the brief main points coming out of this?

We found that the use of temporal suppression with an LHRH analogue during chemotherapy was associated with a statistically significant reduction in the premature ovarian failure rate and with a higher pregnancy rate with no impact on disease free survival although only three studies among the twelve included in our meta-analysis reported disease free survival events.