Side effects of endocrine therapy

Menopause in association with breast cancer

Menopausal symptoms are a common consequence of treatment for breast cancer. Endocrine therapy is often given alongside other treatments (e.g. suppression of ovaries by medical intervention such as goserelin, and/or following adjuvant chemotherapy), all of which may have an effect on women entering an early menopause. The nearer to natural menopause (around the age of 50 years), the more likely it is that menopause will occur and be permanent.

Side effects and the effects of menopause experienced by women with breast cancer can occur as a direct consequence of endocrine therapy.

Tamoxifen and Aromatase Inhibitors have different side effects and are listed below.

Less common side effects include:

• Headaches
• Depression
• Numbness and tingling in the hands and fingers
• Heart palpitations

Management of the most common side effects of endocrine therapies are listed below.

It is important to reassess and evaluate interventions regularly

Hot Flushes
The prevalence and severity of hot flushes is higher in women undergoing treatment for breast

cancer. Hot flushes and night sweats are the most commonly reported vasomotor symptoms. These can range from feeling warm to experiencing intense heat on the upper body and face.

 Practical Advice / Non Pharmacological Management

- Identify and avoid triggers such as caffeine / alcohol / spicy foods / nicotine

- Use fans to cool room/handheld fan for facial cooling

- Use a cooling facial mist spray

- Wear light layers of loose clothing that can be removed

- Have layers of bedclothes that can be removed

- Wear cotton or linen fabrics, avoid manmade materials

- Have cool water available to sip regularly

- Consider the use of a cooling pillow pad for night-time sweats

- Discuss diet / exercise / weight control / stress management and relaxation strategies

 Pharmacological Management:

- Establish frequency / intensity / impact of symptoms on quality of life

- Medication history, particularly the use of over-counter medications and supplements

- Discuss potential triggers and lifestyle advice (e.g. exercise, diet, stress management)

- Consider the use of a menopausal rating scale to assess pre- and post-intervention

 Recommended Prescribed Medication:

- SSRIs (selective serotonin reuptake inhibitors) / SNRIs (selective noradrenaline reuptake

inhibitors), such as venlafaxine 37.5 -75mg/day or citalopram 10-20 mg/day (this is favoured

over paroxetine or fluoxetine for patients taking Tamoxifen).

- Gabapentin (start at 300 mg nocte then titrate to 300 mg three times per day over 9 days)

- Clonidine (0.1 mg/day)

- Oxybutynin 2.5 mg – 5 mg BD

Vaginal dryness

Lowered oestrogen levels result in thinning of the epithelial cells of the vulvovaginal area, the vaginal walls become thinner and loose elasticity. Vaginal dryness can range from mild to severe irritation, causing dyspareunia.

Pharmacological Management:

Consider use of simple moisturisers and gels:

- A polycarbophil moisturising gel such as Replens, can improve vaginal moisture and elasticity.

Use applicator-insert gel three nights a week. Contains no oestrogen, may be retained

in the vagina longer.

- For some women, it may be appropriate to consider the use of local oestrogen for a short

period of time. Oestrogen preparations should be chosen with care as some are larger doses,

which may be absorbed and raise serum oestrogen levels.

Joint pain / Aromatase inhibitor-induced arthralgia

The exact aetiology of this is unknown, however, decreased oestrogen levels is likely to be a main contributory factor. Joint pain has been shown to be a particular problem in women taking aromatase inhibitors (Als), with as many as 82% of women reporting joint pain.

AI –induced arthralgia (AIA) is a relatively new entity, and has been defined in which patients meet all of the following major criteria and at least three minor criteria:

Major criteria

- Currently taking AI therapy

- Joint pain that has developed or worsened since starting AI therapy

- Joint pain improves or resolves within 2 weeks of stopping AI therapy

- Joint pain returns upon resuming AI

Minor criteria

- Symmetrical joint pains

- Pain in hands and/or wrists

- Carpel tunnel syndrome

- Decreased grip strength

- Morning stiffness

- Improvement in joint discomfort with use or exercise

Practical Advice / Non Pharmacological Management

- Counselling and education. The side effects of AIs should be described clearly from the

beginning, and follow-up of symptoms at 2 months and 6 months and further

follow-up as required.

- Lifestyle modifications; weight reduction, regular exercise increasing joint mobility

- Acupuncture

- Massage therapy and relaxation techniques

 Pharmacological Management:

There is little research to date on management of AIA, therefore, management is predominately based on clinical experience:

- To control the discomfort, paracetamol alone should be tried first

- For continued pain add ibuprofen or other nonsteroidal anti-inflammatory drugs (NSAIDs).

- The addition of opioids with or without paracetamol can be used for more severe or

non-responsive pain. Pain modifiers such as tricyclic antidepressants or anticonvulsants may be

added for severe resistant painful arthralgia. For complex management seek specialist pain or

rheumatology consultation.

Cancer treatment-induced bone loss
As a result of suppression of oestrogen levels, pre-menopausal women are at significant risk of accelerated bone loss associated with cancer treatment (including chemotherapy, tamoxifen, and ovarian suppression).

Aromatase inhibitors induced bone loss (AIBL) has been found to occur at over the double the rate of physiological post-menopausal bone mineral density (BMD) loss leading to increased fracture rate in post-menopausal women.

 Monitoring and Management:

- Women most at risk (pre-menopausal undergoing ovarian suppression and post-menopausal

on AIs) the recommendation is to use DEXA scans to monitor bone mineral density (BMD). Bone

markers may also provide a useful adjunct to assessments. A baseline BMD measurement is

recommended and ongoing monitoring of BMD every one to two years.

- A calcium-rich diet

- Vitamin D (1000-2000 IU) daily

- Regular weight-bearing and resistance exercise

- Medications that reduce bone resorption such as bisphosphonates and denosumab.