Menopause After Breast Cancer

Menopause after breast cancer RMO Gordon Ding

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1. Predictors of menopause after breast cancer

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2. Return of ovarian function after adjuvant chemotherapy – use of aromatase inhibitor

Background 

25% Breast Ca – premenopausal 1,2

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+ use of adjuvant chemotherapy

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Long term consequence: Premature menopause + prolonged exposure to risks of menopause

Predicting chemotherapy-induced menopause 

Age at diagnosis Use of adjuvant systemic treatment

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Change in BMI

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Blood markers 3

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Measuring estradiol, LH, FSH, inhibin – only reflects function at that point of time • Unable to predict the return of ovarian function • best marker for return of ovarian fn is menstruation • Serial monitoring may assist in pt selection for AI

Useful Predictors 

AGE 1,2 Age

< 40

>40

Risk %

22-61

76-97

Useful Predictors 

Adjuvant chemotherapy 1,2,4,5   

Cumulative dose Duration of therapy Alkylating agent (E.g. cyclophosphamide) • • •

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No difference between CMF and CEF Younger women less affected 6 – 9 cycles

Rate is lower with anthracycline-based regime • E.g. doxorubicin plus cyclophosphamide • 4 – 6 cycles

Risk of menopause during first year after breast cancer diagnosis 2 

183 premenopausal women 

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T1-3 N0-1 M0, primary surgical resection w Ax dissection Chemotherapy or chemotherapy+tamoxifen or taxmoxifen alone or no treatment.

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Defn -- Menopause

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Data collected: age, BMI, tumour stage, receptor status, radiation treatment, adjuvant treatment and duration of treatment + age at onset of menopause

2.Goodwin, PJ et al. Risk of menopause during the first year after breast cancer diagnosis. J Clin Oncol 17;8; 1999

Risk of menopause during first year after breast cancer diagnosis 

Final multivariate model Variable

P

Age

< 0.00001

Chemotherapy

< 0.00001

Tamoxifen

0.034

Probability of menopause during 1st yr after diagnosis

0.78

0.4

0.15

Return of Ovarian function Up to 11% of woman spontaneously recovers (higher in younger women) 6 One study showed 27% recovery w the use of AI

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Concerns: 1. Anticancer efficacy reduced 2. Risk of unwanted pregnancy 

Managing of this group of patients maybe challenging

? Suggested guideline for AI for early breast cancer after CIA  Baseline evaluations 3   

4 week prior to chemo Estradiol, FSH/LH Ca, DEXA

Age

Blood tests Recommendation

< 40

N/A

If estrogen depletion desired, ovarian suppression with AI

> 40

Serial estadiol, LH/FSH

> 40

Serial estradiol, LH/ FSH

-- post-menopause, (high FSH/LH, estradiol < 10), AI is appropriate; serial monitoring every 6/12 -- w/i pre-menopausal range (N FSH/LH, estradiol > 20), Tamoxifen alone, or Ovarian ablation w tamoxifen; or Ovarian ablation w AI or Refer for SOFT trial 5,6

Suppression of Ovarian Function Trial 7  

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Phase III Study Evaluates the role of ovarian suppression and the role of exemestane (AI) as adjuvant therapy for premenopausal women with endocrine responsive breast cancer OS + tamoxifen OS + exemestane OS + exemestane

v v v

tamoxifen tamoxifen OS + tamoxifen

References 1. Knobf M. The influence of endocrine effects of adjuvant therapy on quality of life outcomes in younger breast cancer survivors. Oncologist 11;96-110 2006 2.Goodwin, PJ et al. Risk of menopause during the first year after breast cancer diagnosis. J Clin Oncol 17;8;2365-70 1999 3.Ganz PA and Greendale GA. Menopause and breast cancer: addressing the secondary health effects of adjuvant chemotherapy J Clin Oncol 19;14;3303-05 2001 4. Welt CK, Shapiro C. Ovarian failure due to anticancer drugs and radiation. UpToDate 5. Krop IE and Winer EP. Ovarian suppression for breast cancer: An effective treatment in search of a home. J Clin Oncol 23;25;5869-72 2005 6. Smith IE, Dowsett M et al. Adjuvant Aromatase inhibitors for early breast cancer after chemotherapy induced amenorrhoea: caution and suggested guidelines. J Clin Oncol 24;16; 2006 7. Australian New Zealand Cancer Trials Group. http://www.anzbctg.org/