Hormonal Treatment For Breast Cancer
Post treatment concernsfor cancer survivors:a focus on breast cancer.
Presentations made byDr Belinda KielyMedical Oncologist Concord Cancer Centreat the March Public Forumof theSydney Survivorship Centre.
Hormonal Treatmentfor Breast CancerDr Belinda KielyMedical Oncologist Concord Cancer Centre
History of hormonal therapy Oophorectomy - 1896– surgeon George Beatson found he could extend the lives ofwomen with metastatic breast cancer by surgically removingtheir ovaries Tamoxifen – 1966– initially developed as a fertility treatment– first used in breast cancer in 1971 Aromatase inhibitors - early 1990s– anastrazole (Arimidex)– letrozole (Femara)– exemestane (Aromasin)
Hormone receptor positivebreast cancer Breast cancer with receptors to the 2 femalehormones – oestrogen and progesterone - on itscells 75% of all breast cancers
Testing for oestrogen receptorsER positiveER negative
Oestrogen ( /-progesterone) can stimulate thegrowth of hormone receptor positive breastcancer Hormone therapies aim to block this stimulation– anti-hormone therapy Treatment options depend on whether or not awoman is in menopause
Menopause When the ovaries stop producing eggs andmenstrual periods end Average age is 51 years (range 45 – 55) Definitions– Peri-menopause (transition) – periods becomeirregular/ less frequent, can last several years– Menopause – no periods for 12 months– Post-menopause – the time after menopause
Sources of oestrogen Before menopause - ovaries After menopause - subcutaneous fat, liver,muscle
Options for anti-hormone therapy Pre-menopausal women– Tamoxifen– Inhibition of estrogen production from the ovaries temporary - monthly zoladex injections permanent - surgical oophorectomy Post-menopausal women– Tamoxifen– Aromatase inhibitors
How do hormone therapies work?Aromataseinhibitorsdecreaseproductionof oestrogenTamoxifenstopsoestrogenattaching tobreast cancercellsWithout oestrogen breast cancer cells are not stimulated to growSmith IE. N Engl J Med 2003;348:2431-2442
Benefits of anti-hormone therapy 5 yrs of anti-hormone therapy reduces the risk of:– breast cancer coming back somewhere else in thebody (metastases / secondaries)– breast cancer returning in the same breast– a new breast cancer in the opposite breast– death from breast cancer The benefits of anti-hormone therapy last wellbeyond the 5 years you take tablets
Benefits of anti-hormone therapy Tamoxifen (compared to no hormonal therapy)– 12% reduction in risk of breast cancer coming back– 9% reduction in risk of death from breast cancer Aromatase Inhibitors (compared to tamoxifen)– Further 3% reduction in risk of breast cancer coming back– Same reduction in risk of death from breast cancer– All three aromatase inhibitors equivalent efficacy
When to start hormonal therapy 4-6 weeks after surgery After chemotherapy During or after radiotherapy
Duration of hormone therapy At least 5 years Tamoxifen 10 yrs better than 5 yrs– Further reduction in breast cancer recurrence and death– Especially if large cancer, node positive, high grade Tamoxifen 5 yrs - AI 5 yrs better than Tamoxifen 5 yrs Aromatase Inhibitor 5 yrs– No data for safety beyond 5 years– Trials completed and results awaited
Tamoxifen 5 yrs v 10 yrs4% less recurrences3% less deaths
Side Effects of anti-hormone therapy Many healthy tissues benefit from oestrogen– vagina, brain, skin and bones Menopausal symptoms can occur when:– oestrogen is blocked from entering healthy tissueby tamoxifen– oestrogen levels are reduced by aromataseinhibitors
Tamoxifen side effects Common– hot flushes (up to 80%, severe in 30%)– vaginal discharge, sexual dysfunction, irregular periods Less common– dry skin, weight gain, mood change Rare– Blood clots (venous thrombosis) (DVT / PE, 3 in 100) Risks - smoking, surgery, previous blood clots, obesity– cancer of the womb (uterus) (4 in 100) women 50yrs; longer duration on treatment– cataracts
Aromatase Inhibitor Side Effects Common– hot flushes– muscle and joint pains and joint stiffness– vaginal dryness, sexual dysfunction Less common– weight gain, mood change Rare– osteoporosis, fractures– cardiovascular risk– elevated cholesterol
Side Effects: AI v Tamoxifen Analysis of 7 studies enrolling 30 023 womenSide EffectAI%Tamoxifen%Risk for AIv tamoxifenNNHBroken bone7.55.21.5 x46 (AI)4.23.41.3 x132 (AI)DVT/PE/blood clot1.63.10.5 x69 (T)Stroke1.41.5equal-Uterus Cancer0.10.50.3 x250 (T)Cardiovascular(heart attack, high cholesterol)NNH Number of people who must receive treatment for 1 person to develop the side effectAmir E, J Natl Cancer Inst 2011;103:1299–1309.
Managing the side effects Changing to a different tablet– tamoxifen to aromatase inhibitor– aromatase inhibitor to tamoxifen– one aromatase inhibitor to another Take a short break from the tablet “drug holiday”
Hot flushes weight loss, exerciseavoid triggers – spicy food, caffeine, alcoholloose cotton clothing, layer clothingcold packs, fanMedications– venlafaxine (Efexor),– gabapentin (Neurontin)– clonidine (Catapress)
Joint pain and stiffness ExerciseAcupunctureyogavitamin Dglucosamineparacetamol, anti-inflammatories
Vaginal Dryness moisturiser (Replens - non-hormonal) Lubricants (Sylk, Astroglide)
Bone thinning and osteoporosis Aromatase inhibitors can cause thinning of thebones, which may increase the risk of bonefractures and osteoporosis Bone mineral density scan– measures the strength and thickness of the bone– Often done when starting an aromatase inhibitorthen repeated every 1-2 years while on treatment
Keeping bones strong Calcium– 3 serves of dairy per day– Supplements eg caltrate Vitamin D– Sunlight, diet (oily fish)– Supplements eg ostelin, ostevit Weight bearing exercise Medications – if previous fractures or establishedosteoporosis– Bisphosphonates eg Fosamax, Aclasta– Denosumab (Prolia)
Compliance Many women stop taking anti-hormonal therapybefore completing 5 yrs One study looked at percentage still onmedication at each year from starting therapy– 1 yr 90%– 3 yrs 77%– 5 yrs 51% Taking tablets for 80% of the recommendedtime increases risk of breast cancer returning
5 yrs of anti-hormone therapy reduces the risk of: – breast cancer coming back somewhere else in the body (metastases / secondaries) – breast cancer returning in the same breast – a new breast cancer in the opposite breast – death from breast cancer The benefits of anti-hormone therapy last well
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Breast cancer development In the United States, breast cancer is the most common cancer diagnosed in women (excluding skin cancer). Men may also develop breast cancer, but less than 1% of all people with breast cancer are men. Breast cancer begins when healthy cells in the breast change and grow uncontrollably, forming a mass called a tumor.
breast cancer, metastases, advanced breast cancer, secondary tumours, secondaries or stage 4 breast cancer. For most people with secondary breast cancer in the brain, breast cancer has already spread to another part of the body such as the bones, liver or lungs. However, for some people, the brain may be the only area of secondary breast cancer.
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breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2) or Lynch syndrome [9]. Previous condition of breast, colorectal or endometrial cancer can lead to ovarian cancer. The age is considering as risk factors. Women aging 55 years or older may develop ovarian cancer due to hormonal changes, in addition
Breast Cancer Breast cancer is one of the most common forms of cancer among women (40,290 in 2015). It is second only to lung cancer as a cause of cancer deaths in American women, One-third of women with breast cancer die from breast cancer, One out of every eight women will be
lung cancer. Breast cancer, as with most cancers, is classified on its extent of spread in the body. Treatment is most successful when breast cancer is discovered early in the localized stage.4 Breast cancer is predominantly a disease affecting women; in 2016, 2,904 women in Florida died of breast cancer.
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