Menopause after breast

cancer

RMO

Gordon Ding
 1. Predictors of menopause after breast cancer

 2. Return of ovarian function after adjuvant

chemotherapy – use of aromatase inhibitor
 Background

 25% Breast Ca – premenopausal 1,2

 + use of adjuvant chemotherapy

 Long term consequence: Premature menopause

+ prolonged exposure to risks of menopause
 Predicting chemotherapy-induced
menopause
 Age at diagnosis
 Use of adjuvant systemic treatment

 Change in BMI

 Blood markers 3
 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)
• 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
 T1-3 N0-1 M0, primary surgical resection w Ax
dissection
 Chemotherapy or chemotherapy+tamoxifen or
taxmoxifen alone or no treatment.

 Defn -- Menopause

 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
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 -- post-menopause, (high FSH/LH,

estadiol, estradiol < 10),
LH/FSH AI is appropriate; serial monitoring
every 6/12
> 40 Serial -- w/i pre-menopausal range (N
estradiol, FSH/LH, estradiol > 20),
LH/ FSH 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
 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 v tamoxifen
 OS + exemestane v tamoxifen
 OS + exemestane v 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/