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Breast cancer and menopause
Managing menopausal symptoms in women with breast cancer may be challenging.
Introduction
Women diagnosed with breast cancer (BC) may develop menopause/menopausal symptoms as a result of:
1) Menopause occurring concurrently with BC diagnosis
2) Menopause occurring secondary to BC treatment (chemotherapy or oophorectomy)
3) Adjuvant endocrine therapy (menopausal symptoms)
4) Cessation of hormone replacement therapy (HRT) upon BC diagnosis (symptom recurrence).Significant short term and long term consequences may be associated with menopause, including menopausal symptoms, psychological distress, sexual dysfunction and potential increased risk of cardiovascular disease and osteoporosis.
Menopausal risk
Approximately 25% of women are premenopausal at the time of BC diagnosis. The incidence of chemotherapy-induced temporary or permanent amenorrhoea (menopause) ranges from 0–100% depending on the woman’s age, type, cumulative dose and duration of chemotherapeutic agent used.
It has been postulated that each month of BC chemotherapy translates into 1.5 years of reproductive life lost.1 The onset of amenorrhoea/menopause may occur abruptly or insidiously with menopausal symptoms occurring while menses persist.2 At present there are no biochemical/ biophysical markers to predict menopause.
Symptoms
The relative contributions of menopause, BC diagnosis and/or treatment to symptomatology are often difficult to determine.3 Younger women who experience menopause report more physical symptoms, psychological distress and poorer sexual functioning compared with other BC survivors.4 Up to 20% of BC women cease/consider ceasing endocrine therapy due to menopausal symptoms.5
Vasomotor symptoms: reported in up to 80% of women with BC, may be more severe and frequent compared to women without BC.6,7 Symptoms may also vary with the type of BC treatment (oophorectomy, chemotherapy, GnRH agonist, tamoxifen and aromatase inhibitors).7-9
Urogenital symptoms: are frequently problematic with 50–75% of BC survivors reporting one or more symptoms;10 especially those taking aromatase inhibitors.
Sexual dysfunction: is reported in 70% of Australian women with BC in a recent prospective study,11 with a decline in sexual activity with time since BC diagnosis also observed.12 Multiple physical, treatment and psycho-social factors influence sexual function in women with BC.4,11,13
Mood and cognitive problems: as well as a reduction in quality of life may be observed.8,12,14 The degree/ pattern of psychological distress varies with age7 and time since diagnosis.15,16 Depression and/or anxiety was observed in almost 50% of BC women,15,17 in the year following diagnosis which persisted in 25% of women at four years.15 Tumour status, treatment, age, co-morbidity and psychosocial factors influence the risk of depression/anxiety.8, 15,18, 1
Sleep disturbance: in menopausal women ranges from 20–70%,20 with vasomotor symptoms an important contributor to insomnia in women with BC.20
Management
Management of menopause in women with BC involves lifestyle modification, psychological support/intervention, pharmacological therapies, prevention/treatment of the long term consequences of menopause and education21 (see Table 1).
Lifestyle: Lifestyle modification may assist menopausal symptom control, psychological symptomatology and cardiovascular and osteoporosis risk reduction.
Vasomotor symptoms: Level 1/2 evidence,22,24,25 indicates that venlafaxine, desvenlafaxine, paroxetine, fluoxetine, citalopram, escitalopram, gabapentin and clonidine are effective in reducing vasomotor symptoms (see Table 2). However, comparative and long term efficacy and safety data is lacking. Importantly, CYP2D6 inducers (e.g. paroxetine and fluoxetine) may interfere with tamoxifen metabolism and should be avoided in women taking tamoxifen with evidence of increased BC recurrence/ mortality.26 Recently, cognitive behavioural therapy has been demonstrated to improve mood and vasomotor symptoms.27 Use of HRT in women with BC is contra-indicated due to increased risk of recurrence.28
Urogenital symptoms: Initially, lifestyle measures, vaginal moisturizers (used chronically to improve vaginal elasticity/ atrophy and lubricants (used prior to sexual intercourse) may be necessary.21
If symptoms persist, consideration should be given to a trial of a vaginal oestriol (not oestradiol) preparation (although the use of vaginal oestrogen and aromatase inhibitors concurrently is controversial) and/or changing to an alternative anti-oestrogen therapy.10, 21
Sexual dysfunction: A multifaceted approach is required including treatment of psychological/relationship issues in addition to urogenital symptoms. Ceasing/changing medication which can negatively impact sexual function, (e.g. antidepressants, aromatase inhibitors) may be necessary. There is no indication for the use of testosterone therapy currently.29
Alternative/complementary therapies: There is a lack of high quality, consistent efficacy and safety data to support the use of therapies including bioidenticals, phyto-oestrogens, herbal preparations, homeopathy, reflexology and body manipulation in the management of menopausal symptoms.24
Mind body interventions including yoga, hypnosis,relaxation therapy and acupuncture show promise but more research is needed.24,30,31
Conclusion
Menopause can negatively impact women with BC. Multidisciplinary menopause clinics, clinical guidelines21 and websites (see below) can assist.
www.managingmenopause.org.au/health-professionals/cpd-menopause-breast-cancer
Table 1: Points to consider when evaluating the menopausal woman with breast cancer
(derived from reference 21)
- Likely cause of menopausal symptoms
- Frequency/severity of menopausal symptoms and impact on quality of life
- Factors triggering/exacerbating symptoms
- What she wishes/ expects from intervention
- Provide information. This may be all she desires
- Assess risk of long term complications e.g. osteoporosis and cardiovascular disease.
Table 2: Non-hormonal vasomotor symptom treatment
(derived from references 22, 24,29)
Preparation Dose Hot flush reduction
Gabapentin 300–900mg/day Up to 66%
Venlafaxine XR 37.5–75mg/day Up to 66%
Paroxetine 10–20mg/day Up to 60%
Fluoxetine 15mg/day 20%
Desvenlafaxine 100mg/day 60%
Citalopram 10–20mg/day 50%
Clonidine 0.1mg/day 26–40%
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