Determining menopausal status in women receiving anti-oestrogen treatment. Luke Hughes-Davies Addenbrookes Hospital, Cambridge

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Gerard Cobb
6 years ago
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1 Determining menopausal status in women receiving anti-oestrogen treatment Luke Hughes-Davies Addenbrookes Hospital, Cambridge

2 Letter from GP 2017 Now that your patients are being discharged back to primary care as soon as they finish chemotherapy...

3 Letter from GP. it would be most helpful if you and your colleagues could develop a consistent and easy to follow policy for hormonal therapy. Your policies seem to change every eighteen months.

4 Letter from GP. and it is becoming difficult to understand what is going on with these patients.

5 In recent years.

6 In recent years. We switched over to aromatase inhibitors, but not for everyone and there were endless debates about sequencing, switching, substitution or extension. (surprisingly the cost issues melted away quite quickly)

7 In recent years. Patients on tamoxifen were suddenly told to take it for ten years instead of five years.

8 In recent years. Ovarian suppression was actively discouraged then it suddenly became important again

9 In recent years. AIs had no role for younger women then we had to start considering them.

10 In recent years. Extended letrozole was headlined in the Daily Mail now we cannot decide if the benefits outweigh the risks

11 In recent years. Our view of Progesterone has changed from please remove this patient s Mirena coil as soon as possible

12 In recent years. to I have prescribed megace at low dose and would be grateful if you could continue this [expensive-unlicensed-and-impossible to obtain] drug in primary care

13 In recent years. Bisphosphonates have come from nowhere to become a mainstay of adjuvant therapy (but only for menopausal patients)

14 In recent years. We have become much more relaxed about pregnancy after breast cancer treatment and actively encourage it.

15 In recent years. We have started to become much more relaxed about our patients becoming pregnant after breast cancer treatment

17 these management decisions often depend on the patients menopause status

20 Most of us were raised on the 80:20 rule of thumb

23 6 months amenorrhoea

24 12 months amenorrhoea

25 24 months amenorrhoea

27 In general, three groups of women can safely be considered postmenopausal

28 All women older than the age of 60,

29 Women who have undergone bilateral oophorectomy

30 Women younger than 60 years amenorrheic for at least one year prior to the diagnosis of breast cancer.

31 Remaining ovarian activity cannot be excluded for all other women and therefore their menopausal status is uncertain.

33 FSH levels > 20 IU/L and estradiol levels in postmenopausal range according to the local laboratory (in general < 110 pmol/l) over 2 3 years of tamoxifen treatment

34 Patients who meet these criteria can be considered truly postmenopausal and be switched from tamoxifen to an AI.

35 After AI initiation, serial monitoring of FSH and estradiol is strongly recommended for at least another year.

36 Even two years of chemo induced amenorrhoea can be falsely reassuring

40 Could AMH make all this easier?

42 pg/ml IU/L AMH ** FSH ** * Menses Amen Trans TA No chemo NC amen Menses Amen Trans TA No chemo NC amen

44 Berlin 1830

47 Alfred Jost Paris 1945

48 Normal anatomy of male and female rabbits

49 Effects of castrating either a male or female rabbit

50 Grafting testicular tissue into female foetus

52 Boston and Liverpool 1972 Patricia Donohoe

54 Anti-Müllerian Hormone is expressed in small but not larger follicles AMH Estradiol So shows minimal variation across the menstrual cycle

55 MH is a follicular gatekeeper limiting follicle growth initiation, and subsequently estradiol production from small antral follicles prior to selection.

56 Years to final menses AMH related to both time to and age at Final Menses

57 Years to final menses But early assays too insensitive to get close enough

58 This has led the OPTIMA trialists to team up with Richard Anderson

59 to come up with a study to examine the diagnosis of menopause

60 Diamond Diagnosing menopause for Oncology Decisions

61 Diamond A non-randomised intervention study

62 Diamond which uses a high-sensitivity AMH assay

63 Diamond to determine menopausal status in women with post-chemotherapy amenorrhoea

65 DIAMOND Sample size 500 patients

66 DIAMOND Primary endpoint Incidence of menopause at 12 months post chemotherapy

67 DIAMOND Hypothesis End of chemotherapy hormone profile predicts menopause with accuracy of >90%

Study Of Letrozole Extension. Coordinating Group IBCSG IBCSG BIG 1-07

Study Of Letrozole Extension. Coordinating Group IBCSG IBCSG BIG 1-07 tudy Of Letrozole Extension Coordinating Group IBCSG IBCSG 35-07 BIG 1-07 A phase III trial evaluating the role of continuous letrozole versus intermittent letrozole following 4 to 6 years of prior adjuvant