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Breast Cancer Survivors: Menopausal Symptom Management

by Dr. Richard J. Santen, Professor of Medicine, Division of Endocrinology
University of Virginia

How to cope with menopausal symptoms if you are a breast cancer survivor

 

Introduction

Early diagnosis and more effective treatments have markedly reduced the death rate from breast cancer over the past 20 years. For this reason, the number of women surviving after a diagnosis of breast cancer is increasing, now reaching 3.1 million in the USA and 9.3 million worldwide. The majority of survivors have undergone menopause spontaneously or as result of breast cancer therapy. Estrogen, the major female hormone, falls to low levels at menopause and thereafter. While a lack of this hormone causes symptoms in 80-95% of survivors, effective methods to manage these problems are available.

What are the most important problems? Hot flashes may be moderate or severe and result in difficulty with frequent awakening at night and as a consequence, fatigue, mild depressive symptoms and mood changes. Hot flashes during the daytime are bothersome and may also interfere with work and social interactions. Bone pain or rapid loss of bone may take place, resulting in spontaneous or fall-related bone fractures. Loss of estrogen causes thinning of the vaginal tissues and can result in itching, infections, burning, and pain on intercourse.  Less common problems include weight gain, symptoms of degenerative arthritis (i.e. arthritis commonly associated with aging), pain from disk disease in the spine, aging-type skin changes, and reduced quality of life. Other problems such as cardiovascular disease can be made worse by breast cancer treatments such as   chemotherapy, radiation, anti-estrogens or drugs to block the formation of estrogens (i.e. aromatase inhibitors).

How can these problems be managed? 

The most important principle is to tailor the treatment specifically for each patient based on the degree of bother related to the symptoms and the severity of bone loss and damage to other estrogen dependent tissues. For mild symptomatology and lack of objective signs of damage to tissues, lifestyle modifications or over the counter options may be sufficient. Moderate or severe signs or symptoms usually require pharmacological management.

Lifestyle modifications:  Simple measures such as lowering of room temperature, using portable fans, dressing in layers that can be easily shed, avoiding triggers (such as spicy foods and stressful situations) weight loss  and exercise, may help reduce the number of hot flashes. Non-drug-like agents such as soy, black cohosh, flaxseed, remifemin, equol in equol -producers, vitamin E, and acupuncture may be helpful for hot flashes when mild. Methods such as stress management, relaxation, deep breathing, and yoga may also be helpful. As approximately 30% of women respond to placebos, some of the effects of these strategies may be placebo (i.e. sugar pill ) effects.

All survivors of breast cancer need to follow general health maintenance programs such as increased physical activity, weight reduction, stopping smoking, and giving up alcohol. Physical activity improves balance, the amount of fat in your body, muscle strength, and bone health; improves mood; reduces cardiovascular risk; and potentially, reduces falls which can result in broken bones (factures). As obesity, independent of treatment, is associated with a poorer prognosis after breast cancer, getting to a normal body weight is to be encouraged. Another lifestyle modification is for you to have enough vitamin D from sunlight and pills and to take enough calcium to maintain bone health. The Institute of Medicine, a prestigious medical advisory group, recommends that you take at least 1200 mg of calcium and 700-800 International Units (IU) of vitamin D daily.

Management of moderate or severe signs and symptoms:

Hot flashes: While the most effective treatment of moderate to severe hot flashes is the use of estrogen preparations, this approach is usually not recommended in women with a history of breast cancer because this may be harmful. However, there are a variety of non-estrogen drugs which can be helpful including several drugs usually prescribed for depression (i.e. SSRN, SNRI drugs) but effective for hot flashes. These agents result in an overall 70-80% improvement in hot flash number and severity. However, on average, approximately 30% of the improvement is due to placebo effects. However, from your point of view, overall benefit (including both drug and placebo effect) is the most important factor with respect to reduction of hot flash severity, problems with sleep, improvement in mood and quality of life. A great deal of clinical experience has been gained by the numerous studies of Dr.Charles Loprinzi and his group at the Mayo Clinic in breast cancer survivors. The first recommendation from this group is for you to try low dose antidepressants such as venlafaxine, desvenlafaxine, escitalopram and paroxetine. If you are taking tamoxifen, you should avoid certain of these agents such as Prozac or Zoloft at the advice of your health care provider as these agents can reduce the efficacy of tamoxifen.

Nighttime hot flashes may be associated with a greater risk of minor depression, fatigue, and mood changes than those occurring during the daytime. On this basis, the first step in management is to find out whether your symptoms occur mostly at night as the pattern of hot flash presentation can determine the specific therapy to be chosen. For night time hot flashes or sleep disruption, a single dose of gabapentin given one hour before sleep is associated with a reduction in night time hot flashes and is helpful in putting you to sleep. Gabapentin lasts in your body for only a few hours so that few side effects are present upon awakening. Clinical experience has shown that the gabapentin dose must be individually determined with one dose ranging from 100 mg to 1200 mg given one hour before bedtime. You will usually start with a low dose and then gradually increase until the hot flashes are better. For hot flashes occurring both during the day and night, an additional morning dose of gabapentin can be added. 

A key question is whether or not menopausal hormone therapy such as estrogen might be prescribed to breast cancer survivors who are not benefitted by the drugs mentioned above. Several expert groups have recommended that estrogen therapy can be used in the lowest effective dose but only after obtaining full, written  informed consent from you with attention to all potential risks and benefits. One expert guideline states “A fully informed patient should be empowered to make a decision that best balances individual quality of life benefits against potential health risks.”

Problems associated with vaginal atrophy: Symptoms include vaginal dryness, irritation, itching, infection, discomfort and painful sex (dyspareunia). Dyspareunia in turn leads to diminished sexual desire, arousal difficulties, and relationship problems. For mild symptoms, regular use of vaginal moisturizers used chronically in combination with  lubricants used at the time of intercourse may be effective for you. Very low dose vaginal estrogen should be used cautiously and only in consultation with a breast oncologist.

Depressive symptoms and mood changes: Recent studies support the concept that mild depressive symptoms and fatigue may in part result from sleep disruption with frequent awakening at night due to hot flashes. Gabapentin or its sister drug, pregabalin, may be used for these symptoms. Moderate or severe depression requires the use of more rigorous measures such as use of antidepressants or psychiatric care.

Cognition: Menopause is associated with subtle changes in thinking and memory and particularly, memory for specific words. Problems with sleep may contribute as sleep is important for various types of memory and sleep health techniques and medications are available to facilitate sleep.

Osteopenia, Osteoporosis, and Fractures: Several approaches can be used to prevent broken bones (fractures) and to improve the amount of bone you have. Preventative treatment  agents include oral and parenteral bisphosphonates (alendronate, ibandronate, risedronate, zoledronic acid)  and an antibody blocker called denosumab or Prolia. Problems with these medications include delayed healing of teeth if you have dental problems and atypical fractures of the leg. A medical care provider should council you whether or not you should use one of these. A method to determine your risk of fracture, called FRAX, can be used to see if you are at high risk of fracture and can guide decision making about use of these.

Cardiovascular disease: Breast cancer survivors may be at high risk of cardiovascular disease and can benefit from a statin drug. Emphasis on cessation of smoking, maintenance of a healthy body weight, nutritious dietary pattern, regular exercise, and aggressive treatment of traditional risk factors such as hypertension and high glucose levels also represents appropriate approaches. 

Conclusions: managing of menopausal symptoms in breast cancer survivors requires a comprehensive approach and individualization of therapy tailored to each patient.

 


 

Dr. Richard Santen is a Professor of Medicine in the Division of Endocrinology at the University of Virginia and has an active clinical practice. His research interests have focused on the development of aromatase inhibitors for treatment of breast cancer, mechanisms relating estrogens to breast cancer, the biology and natural history of endocrine-dependent breast cancer, and the effects of vaginal estrogens on circulating hormone levels. He has published over 400 manuscripts and chapters, predominantly related to the role of estrogen in breast cancer development and treatment. He has been funded consecutively by the National Institutes of Health for over three decades.  For his work in the development of aromatase inhibitors, he received the Susan Komen Foundation Brinker International Award for breast cancer clinical research. Other awards include the Clinical Chemistry Distinguished Science Award, the Robert H. Williams Distinguished Leadership Award of the Endocrine Society, and the William L. McGuire Memorial Lectureship Award for breast cancer. Elected professional memberships include the American Society for Clinical Investigation and the Association of American Physicians. He is a long standing member of the American Society of Oncology (ASCO). He was President of the Endocrine Society in 2015, an organization with 17,000 members.

 


 

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