Menopause After Breast Cancer

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Menopause after breastMenopause after breastcancercancer

RMORMO

Gordon DingGordon Ding


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1. Predictors of menopause after breast cancer1. Predictors of menopause after breast cancer

2. Return of ovarian function after adjuvant2. Return of ovarian function after adjuvant

chemotherapy use of aromatase inhibitorchemotherapy use of aromatase inhibitor


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BackgroundBackground

25% Breast Ca premenopausal25% Breast Ca premenopausal 1,21,2

+ use of adjuvant chemotherapy+ use of adjuvant chemotherapy

Long term consequence:Long term consequence: Premature menopausePremature menopause

+ prolonged exposure to risks of menopause+ prolonged exposure to risks of menopause


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Predicting chemotherapy-inducedPredicting chemotherapy-induced

menopausemenopause Age at diagnosisAge at diagnosis Use of adjuvant systemic treatmentUse of adjuvant systemic treatment

Change in BMIChange in BMI

Blood markersBlood markers 33 Measuring estradiol, LH, FSH, inhibin only reflectsMeasuring estradiol, LH, FSH, inhibin only reflects

function at that point of timefunction at that point of time Unable to predict the return of ovarian functionUnable to predict the return of ovarian function best marker for return of ovarian fn is menstruationbest marker for return of ovarian fn is menstruation Serial monitoring may assist in pt selection for AISerial monitoring may assist in pt selection for AI


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Useful PredictorsUseful Predictors

AGEAGE 1,21,2

76-9722-61Risk

%

>40< 40Age


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Risk of menopause during first yearRisk of menopause during first year

after breast cancer diagnosisafter breast cancer diagnosis 22

183 premenopausal women183 premenopausal women T1-3 N0-1 M0, primary surgical resection w AxT1-3 N0-1 M0, primary surgical resection w Ax

dissectiondissection Chemotherapy or chemotherapy+tamoxifen orChemotherapy or chemotherapy+tamoxifen or

taxmoxifen alone or no treatment.taxmoxifen alone or no treatment.

Defn -- MenopauseDefn -- Menopause

Data collected: age, BMI, tumour stage, receptorData collected: age, BMI, tumour stage, receptorstatus, radiation treatment, adjuvant treatmentstatus, radiation treatment, adjuvant treatmentand duration of treatment + age at onset ofand duration of treatment + age at onset ofmenopausemenopause

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

17;8; 1999


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Risk of menopause during first yearRisk of menopause during first year

after breast cancer diagnosisafter breast cancer diagnosis

Final multivariate modelFinal multivariate model

0.034Tamoxifen

< 0.00001Chemotherapy

< 0.00001Age

PVariable


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Return of Ovarian functionReturn of Ovarian function

Up to 11% of woman spontaneously recoversUp to 11% of woman spontaneously recovers

(higher in younger women)(higher in younger women) 66

One study showed 27% recovery w the use ofOne study showed 27% recovery w the use of

AIAIConcerns:Concerns:

1. Anticancer efficacy reduced1. Anticancer efficacy reduced

2. Risk of unwanted pregnancy2. Risk of unwanted pregnancy

Managing of this group of patients maybeManaging of this group of patients maybe

challengingchallenging


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? Suggested guideline for AI for early? Suggested guideline for AI for early

breast cancer after CIAbreast cancer after CIA

Baseline evaluationsBaseline evaluations 33

4 week prior to chemo4 week prior to chemo Estradiol, FSH/LHEstradiol, FSH/LH

Ca, DEXACa, DEXA


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-- w/i pre-menopausal range (N

FSH/LH, estradiol > 20),

Tamoxifen alone, or

Ovarian ablation w tamoxifen; or

Ovarian ablation w AI or

Refer forSOFT trial 5,6

Serial

estradiol,

LH/ FSH

> 40

-- post-menopause, (high FSH/LH,

estradiol < 10),

AI is appropriate; serial monitoring

every 6/12

Serial

estadiol,

LH/FSH

> 40

If estrogen depletion desired, ovariansuppression with AIN/A< 40

RecommendationBlood testsAge


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Suppression of Ovarian Function TrialSuppression of Ovarian Function Trial77

Phase III StudyPhase III Study

Evaluates the role of ovarian suppression andEvaluates the role of ovarian suppression and

the role of exemestane (AI) as adjuvant therapythe role of exemestane (AI) as adjuvant therapy

for premenopausal women with endocrinefor premenopausal women with endocrineresponsive breast cancerresponsive breast cancer

OS + tamoxifenOS + tamoxifen vv tamoxifentamoxifen OS + exemestaneOS + exemestane vv tamoxifentamoxifen

OS + exemestaneOS + exemestane vv OS + tamoxifenOS + tamoxifen


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ReferencesReferences

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 20014. 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; 20067. Australian New Zealand Cancer Trials Group. http://www.anzbctg.org/

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Menopause After Breast Cancer