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Follow-up after treatment for breast cancer in young women
The Breast (2006) 15(S2) S71–S75
www.elsevier.com/locate/breast
Follow-up after treatment for breast cancer in young women Nicola Roche Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK
KEYWORDS Young; Breast cancer; Follow-up
Summary The majority (80%) of breast cancers are diagnosed in women over the age of 50; only 5% will be in their 20s and 30s. These women have specific needs that include genetic counselling, psychological support, advice with regard to fertility and pregnancy issues and information on coping with treatment-related morbidity. The primary purpose of follow-up is often regarded as the early detection of recurrence as well as the detection of second primary tumours. Rather than concentrating solely on detecting cancer recurrence, clinicians need to be more susceptive to symptoms related to treatment morbidity and to the information needs of their patients. This paper outlines the specific issues listed above that need to be addressed in followup clinics and highlights interventions that may help improve the value of follow-up appointments and quality of life for young women with breast cancer. © 2006 Elsevier Ltd. All rights reserved.
Introduction Providing routine follow-up care for breast cancer patients is standard practice in most countries. The primary purpose of follow-up is often regarded as the early detection of recurrence as well as the detection of second primary tumours. Whether this is actually achieved by routine continuous follow-up or indeed whether early detection has an impact on quality of life or survival is controversial 1 . In addition, no consensus exists as to the duration and frequency of followup 2,3 , what investigations should be performed or indeed where (hospital or primary care) 4,5 and which type of health professional (doctors or nurses) 6,7 should provide follow-up care. Many authors have questioned the value of followup 1,8,9 but there is a dearth of prospective trials evaluating its efficacy 10 . This paper will not address the controversial aspects of follow-up. The aim is to address issues that particularly relate to the younger patient. There is an increasing
awareness that follow-up appointments should concentrate more on the morbidity of treatment, the provision of information and reassurance as well as addressing psychological concerns. Many of these issues are of greater significance to the younger breast cancer patient. The number of women with breast cancer under the age of 40 in the UK has risen by 50% since 1975 11 , and as the mortality of breast cancer continues to fall there are greater numbers of young breast cancer survivors. Many of the anxieties that follow a diagnosis of breast cancer are the same for both younger and older women such as fear of dying and cosmetic concerns. Younger women often have additional issues to contend with and these will be dealt with below.
Genetics The majority of breast cancers are sporadic with only 5–10% being due to high-risk susceptibility genes, but this proportion varies with age.
0960-9776/$ - see front matter © 2006 Elsevier Ltd. All rights reserved.
S72 In women in their 20s approximately 33% of breast cancers will be due to genetic mutations, decreasing to 22% in women in their 30s 12 . Particular care therefore needs to be given to a woman’s family history and if appropriate she should be referred for genetic counselling and testing. If a young patient has a strong family history of breast cancer she may have seen her mother or other close relative go through treatment and possibly die. This will have a great influence on the treatment decisions she makes. The risk of contra-lateral breast cancer in women with BRCA1 or 2 mutations is approximately 40% at 10 years versus 5–10% in sporadic cases 13 . Similarly, their risk of ovarian cancer will be increased. These factors will also have an impact on treatment planning and decisions. In addition, genetic counselling is relevant with regard to young children the patient may have or wish to have. In the UK the Human and Fertilisation and Embryology Authority has recently ruled that preimplantation genetic diagnosis will be allowed for women with BRCA1 or BRCA2 mutations. Currently, there are limited choices for risk reduction in young high-risk women, but these include chemoprevention with tamoxifen 14 and surgery, either mastectomy or bilateral salpingo-oophorectomy.
Surveillance for local recurrence and contra-lateral cancers Guidelines vary as to the optimal period of followup, but all recommend regular mammographic screening and caution against intensive follow-up with blood tests and bone scans, etc. However, the sensitivity of mammography in women under 40 is low due to the increased parenchymal density of the young breast. Only about 45% of young women will have had their cancer diagnosed by mammography, the mammogram being reported as either normal or benign in the remainder 15 . There is evidence that young age is an independent risk factor for local recurrence 16 and the risk of contralateral breast cancer is about 0.6% per year, but is increased greatly in BRCA carriers. Younger women therefore need close surveillance, but the optimal tool for screening for local recurrence and contra-lateral cancers has yet to be determined. Digital mammography has been shown to be more accurate in the young and dense breast 17 . Breast ultrasound is the imaging modality of choice in symptomatic women under 35 years, but it is not recommended as a screening tool and its role in breast cancer surveillance to complement
N. Roche mammography in young women has not been evaluated. MRI is increasingly used in screening highrisk women and it is also useful in distinguishing scarring from recurrence when mammography and ultrasound have been indeterminate 18,19 .
Fertility and future pregnancy Increasing numbers of women are delaying childbirth till their late 30s or early 40s; therefore, the potential loss of fertility as a result of treatment may contribute greatly to the emotional distress of a breast cancer diagnosis. Adjuvant therapies that may affect fertility are chemotherapy, tamoxifen and ovarian ablation. Tamoxifen in itself does not directly cause infertility, but women are advised not to get pregnant while taking tamoxifen. Fertility declines with age and currently we advise women to take tamoxifen for five years. The risk of infertility with chemotherapy will depend on the patient’s age and her ovarian reserve as well as the chemotherapy regime. Most data on chemotherapyrelated amenorrhea (CRA) comes from women having CMF 20 ; the rates of amenorrhea with anthracycline-based regimes are lower. In a series from MD Anderson, none of the patients under 30 developed CRA whereas rates of 33% were reported in women in their 30s 21 . There are limited data on newer agents such as taxanes, although they may incur higher rates of CRA. The return of menstruation following chemotherapy does not equate with fertility and there is evidence that ovarian reserve is depleted despite continued menstruation during chemotherapy 22 . Similarly, even if a woman continues to menstruate during chemotherapy, she is still likely to experience a premature menopause. There is some evidence that medically shutting down the ovaries during chemotherapy with goserelin may preserve fertility 23 , but research to validate this is still on-going. There are very little data to adequately inform women of the potential risks of undergoing fertility treatment either after treatment for breast cancer or at the time of diagnosis and before adjuvant systemic therapy starts. In the latter situation or in women who have become infertile following treatment there are three options to consider: cryopreservation of embryos, oocytes or ovarian tissue. Embryo cryopreservation requires a partner and both oocyte and ovarian tissue cryopreservation are still very much experimental, with only a few successful case reports 24,25 . Embryo cryopreservation requires ovarian hyperstimulation, which is pharmacologically induced
Follow-up after treatment for breast cancer in young women by causing an oestradiol surge. In attempts to avoid this surge in breast cancer patients naturalcycle IVF has been used, but the embryo yield is very low. Recently, tamoxifen and letrozole have been used in conjunction with FSH for ovarian stimulation and it has been demonstrated that embryo yield is as good as conventional FSH stimulation in non-cancer patients with significantly lower oestradiol peaks 26 . Current advice with regard to future pregnancy following breast cancer treatment is to wait at least two years. Results mainly from retrospective studies indicate that there is no significantly increased risk of recurrence as a result of future pregnancies 27 . As indicated above, little data exist on which to base advice for women on the risks of fertility treatment and future pregnancy, so it is vital that the multi-disciplinary team looking after young women facing the prospect of unwanted infertility have access to expert advice from fertility specialists dealing with breast cancer patients.
Hot flushes Hot flushes are experienced by more than 50% of menopausal women. The majority of young breast cancer patients will receive chemotherapy and therefore are at risk of a premature menopause. In addition, tamoxifen and ovarian ablation will cause hot flushes. Hot flushes are a major cause of morbidity in breast cancer patients and along with other menopause and treatment-related symptoms, they may make a young patient “feel old before her time” 28 . The symptoms are often considerably worse than those following a natural menopause 29 . Oestrogen replacement in the form of hormone replacement therapy (HRT) is the best way of treating the vasomotor symptoms, but its safety in breast cancer patients is unknown. Three trials were set up to address this question, one in the UK and two in Sweden, the HABITS trial and the Stockholm trial. The HABITS trial was terminated early as there was an increased number of recurrences in breast cancer patients on HRT compared with controls. This was not demonstrated in the Stockholm study, but it, like the UK study, was closed due the results of the HABITS trial 30 . Uncertainty therefore remains about the safety of HRT in breast cancer patients and its use is generally not recommended. Many alternatives are used and include relaxation techniques, acupuncture, herbs, isoflavones, medroxyprogesterone, megestrol acetate and nonhormonal medicines such as clonidine, gabapentin
S73
and venlafaxine, but there is little evidence to support their efficacy in many instances. As with HRT there are safety concerns with most alternatives. A recent systematic review and meta-analysis on the use of non-hormonal therapies concluded that there was some evidence to support the use of paroxetine, venlafaxine and gabapentin, but the adverse effects restrict the use in many women 31 . There is also a safety issue with the selective serotonin uptake inhibitors as they may interfere with tamoxifen metabolism 32 . The meta-analysis failed to find evidence to support the use of isoflavones 31 . Likewise, there are safety concerns with regard to their use in breast cancer patients 33 . The use of acupuncture has been shown to reduce the number of hot flushes, but the benefits are not usually sustained 34,35 , although the use of self-acupuncture after initial treatment has been reported to provide symptom control for prolonged periods 36 . Unfortunately, there is no well-tolerated, safe and efficacious treatment for the management of hot flushes. Young women will need advice about the different preparations. HRT provides the best relief of symptoms whereas consistent evidence for the use of herbs and isoflavones is lacking 31,37,38 . The use of progestogens and non-hormonal preparations listed above is often restricted by additional unpleasant side effects. The potential benefits in terms of quality of life need to be weighed up against the unquantifiable risk of a taking something that may precipitate disease recurrence. Relaxation techniques and acupuncture, which are entirely safe, do appear to have some benefits, but further evaluation is needed 36-39 .
Premature menopause As well as hot flushes, many women will experience and suffer other symptoms and consequences of therapy-induced menopause such as osteoporosis, lack of libido, vaginal dryness, mood swings, lack of concentration and short-term memory loss. These side effects are often worse in young women than in post-menopausal women having the same treatment 40 . Bone mineral density should be monitored in young women who have experienced a premature menopause and algorithms can be used to guide management 41 . Testosterone has been used to treat lack of libido, but long-term safety data are unknown 42 . Topical oestrogens are effective in relieving symptoms of vaginal atrophy, but again safety data in hormone-sensitive breast cancer patients are lacking. Systemic absorption is unpredictable and if a patient is taking an aromatase
S74 inhibitor there are theoretical concerns that raised oestrogen levels may abolish any beneficial effects of the aromatase inhibitor. Some women find non-hormonal vaginal lubricants helpful. As with the management of hot flushes, young women need to be given information about options for improving symptoms and the theoretical risks need to be balanced against quality of life issues. Protecting themselves against cancer recurrence is a major goal for most women and often they chose to tolerate symptoms rather than take something that is perceived to potentially increase the risk of recurrence 43 .
Psychosocial problems Body image and sexuality fears such as weight gain, hair loss and disfigurement are common to all women with breast cancer, but younger women are at greater risk of anxiety, depression and reduced quality of life. Women under the age of 35 comprise only 5% of breast cancer cases. A sense of isolation is therefore a key issue for many of these young women. They often feel cheated of a planned future and there may be a sense of loss or anger. If they have young children there is a fear that they will not see them grow up 44 . Fatigue is a very common symptom following breast cancer treatment and this can lead to difficulties in returning to work and possible financial problems. Those women who do not have jobs are still the primary home-maker and carer for the children. Depression can develop as a result of feeling inadequate or being unable to carry out this role as well as prior to the diagnosis and treatment for breast cancer. Healthcare professionals need to be alert to signs and symptoms of depression so that escalation into a major depressive illness can be prevented. Patients should be referred for counselling or psychiatric support where needed. Often the most valued intervention in dealing with the fear and isolation experienced by young women is access to peer support groups 44 .
Conclusions Only a small proportion of the many women under follow-up for breast cancer are women who were diagnosed and treated in their 20s or 30s. These young women, nonetheless, have a number of particular issues that need to be addressed in follow-up clinics. It has been shown that doctors are not particularly good at eliciting symptoms related to treatment morbidity 45 . Rather than concentrating solely on detecting cancer recurrence, clinicians need to be more susceptive
N. Roche to symptoms related to treatment morbidity and to the information needs of their patients. Endocrine symptom check-lists and psychological assessments should be carried out at consultations as appropriate. Large numbers of young women who are living with breast cancer and the menopause use complementary and alternative medicine in order to enhance survival and treat symptoms. They need access to evidence-based information to improve outcome and quality of life. Menopause and fertility questions are highly rated by patients, particularly in the follow-up period 46 . Fertility issues, despite being highly rated, are often not discussed or trivialised by health professionals 44,46 . These women should be managed by an extended multi-disciplinary team that includes genetics counsellors, fertility experts, psychologists and social workers. They should also all have access to support groups specific to young women.
References 1. De Bock GH, Bonnema J, van Der Hage J, Kievit J, van de Velde CJH. Effectiveness of routine visits and routine tests in detecting isolated locoregional recurrences after treatment for early-stage invasive breast cancer: a meta-analysis and systematic review. J Clin Oncol 2004;22:4010–8. 2. Guidance on cancer services. Improving outcomes in breast cancer. Manual update. NICE; 2002. 3. Smith TJ, Davidson NE, Schapira, et al. American Society of Clinical Oncology 1998. Update of recommended breast cancer surveillance guidelines. J Clin Oncol 1999;17:1080–2. 4. Grunfeld E, Levine MN, Julian JA, et al. Randomised trial of long-term follow-up for early stage breast cancer: a comparison of family physician versus specialist care. J Clin Oncol 2006;24:848–55. 5. Jiwa M, Thompson J, Coleman R, Reed M. Breast cancer follow-up: could primary care be the right venue? Curr Med Res Opin 2006;22:625–30. 6. Corner J. The role of nurse-led care in cancer management. Lancet Oncol 2003;4:631–6. 7. Koinberg IL, Fridlund B, Engholm GB, Holmberg L. Nurse-led follow-up on demand or by a physician after breast cancer surgery: a randomised study. Eur J Oncol Nursing 2004;8:109–17. 8. Brada M. Is there a need to follow-up cancer patients? Eur J Cancer 1995;31A:655–7. 9. Donnelly J, Mack P, Donaldson LA. Follow-up of breast cancer: time for a new approach. Int J Clin Pract 2001; 55:431–3. 10. Collins RF, Bekker HL, Dodwell DJ. Follow-up care of patients treated for breast cancer: a structured review. Cancer Treat Rev 2004;30:19–35. 11. http://info.cancerresearchuk.org 12. Claus EB, Schildkaut JM, Thompson WD, Neil J. The genetic attributable risk of breast and ovarian cancer. Cancer 1996;77:2318–24. 13. Metcalfe K, Lynch HT, Ghadirian P, et al. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 2004;15:2328–35.
Follow-up after treatment for breast cancer in young women 14. Cuzick J, Powles T, Veronesi U, et al. Lancet 2003;361: 296–300. 15. Ashley S, Royle GT, Corder A, et al. Clinical, radiological and cytological diagnosis of breast cancer in young women. Br J Surg 1989;76:835–7. 16. De Bock GH, van der Hage JA, Putter H, Bonnema J, Bartelink H, van de Velde CJ. Isolated loco-regional recurrence of breast cancer is more common in young patients and following breast conservation therapy: long-term results of European Organisation for Research and Treatment studies. Eur J Cancer 2006;42:351–6. 17. Pisano ED, Gatsonis C, Hendrick E, et al. Diagnostic performance of digital versus film mammography for breast cancer screening. N Engl J Med 2005;353: 1773–83. 18. Kriege M, Brekelmans CT, Boetes C, et al. Efficacy of MRI and mammography for breast cancer screening in women with a familial or genetic predisposition. N Engl J Med 2004;351:427–37. 19. Leach MO, Boggis CR, Dixon AL, et al. Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS). Lancet 2005;365(9473):1769–78. 20. Bines J, Oleske DM, Cobleigh MA. Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol 1996; 14:1718–29. 21. Hortobagyi GN, Budzar AU, Marcus CE, Smith TL. Immediate and long-term effects of adjuvant chemotherapy regimes containing doxorubicin in trials at MD Anderson Hospital and Tumour Institute. NCI Monogr 1986:105–9. 22. Bath LE, Wallace WH, Shaw MP, et al. Depletion of ovarian reserve in young women after treatment for cancer in childhood: detection by anti-mullerian hormone, inhibin B and ovarian ultrasound. Hum Reprod 2003;18:2368–74. 23. Blumenfeld Z. Ovarian rescue/protection from chemotherapeutic agents. J Soc Gynecol Investig 2001;8:S60–4. 24. Porcu E, Venturoli S. Progress with oocyte cryopreservation. Curr Opin Obstet Gynecol. 2006;18:273–9. 25. Donnez J, Dolmanns MM, Demylle D, et al. Restoration of ovarian function after orthotopic (intraovarian and periovarian) transplantation of cryopreserved ovarian tissue in a woman treated by bone marrow transplantation for sickle cell anaemia: case report. Hum Reprod 2006;21:183–8. 26. Oktay K, Buyuk E, Libertella N, Akar M, Rosenwaks Z. Fertility preservation in breast cancer patients: a prospective controlled comparison of ovarian stimulation with tamoxifen and letrozole for embryo cryopreservation. J Clin Oncol 2005;23:4347–53. 27. Clark RM, Chua T. Breast cancer and pregnancy: the ultimate challenge. Clin Oncol R Coll Radiol 1989;1: 11–8. 28. Breast Cancer Care. Standards of care for younger women. 29. Harris PF, Remington PL, Trentham-Dietz A, Allen CI, Newcomb PA. Prevalence and treatment of menopausal symptoms among breast cancer survivors. J Pain Symptom Manage 2002;23:501–9. 30. Holmberg L, Anderson H; for the HABITS steering
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www.elsevier.com/locate/breast
Follow-up after treatment for breast cancer in young women Nicola Roche Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK
KEYWORDS Young; Breast cancer; Follow-up
Summary The majority (80%) of breast cancers are diagnosed in women over the age of 50; only 5% will be in their 20s and 30s. These women have specific needs that include genetic counselling, psychological support, advice with regard to fertility and pregnancy issues and information on coping with treatment-related morbidity. The primary purpose of follow-up is often regarded as the early detection of recurrence as well as the detection of second primary tumours. Rather than concentrating solely on detecting cancer recurrence, clinicians need to be more susceptive to symptoms related to treatment morbidity and to the information needs of their patients. This paper outlines the specific issues listed above that need to be addressed in followup clinics and highlights interventions that may help improve the value of follow-up appointments and quality of life for young women with breast cancer. © 2006 Elsevier Ltd. All rights reserved.
Introduction Providing routine follow-up care for breast cancer patients is standard practice in most countries. The primary purpose of follow-up is often regarded as the early detection of recurrence as well as the detection of second primary tumours. Whether this is actually achieved by routine continuous follow-up or indeed whether early detection has an impact on quality of life or survival is controversial 1 . In addition, no consensus exists as to the duration and frequency of followup 2,3 , what investigations should be performed or indeed where (hospital or primary care) 4,5 and which type of health professional (doctors or nurses) 6,7 should provide follow-up care. Many authors have questioned the value of followup 1,8,9 but there is a dearth of prospective trials evaluating its efficacy 10 . This paper will not address the controversial aspects of follow-up. The aim is to address issues that particularly relate to the younger patient. There is an increasing
awareness that follow-up appointments should concentrate more on the morbidity of treatment, the provision of information and reassurance as well as addressing psychological concerns. Many of these issues are of greater significance to the younger breast cancer patient. The number of women with breast cancer under the age of 40 in the UK has risen by 50% since 1975 11 , and as the mortality of breast cancer continues to fall there are greater numbers of young breast cancer survivors. Many of the anxieties that follow a diagnosis of breast cancer are the same for both younger and older women such as fear of dying and cosmetic concerns. Younger women often have additional issues to contend with and these will be dealt with below.
Genetics The majority of breast cancers are sporadic with only 5–10% being due to high-risk susceptibility genes, but this proportion varies with age.
0960-9776/$ - see front matter © 2006 Elsevier Ltd. All rights reserved.
S72 In women in their 20s approximately 33% of breast cancers will be due to genetic mutations, decreasing to 22% in women in their 30s 12 . Particular care therefore needs to be given to a woman’s family history and if appropriate she should be referred for genetic counselling and testing. If a young patient has a strong family history of breast cancer she may have seen her mother or other close relative go through treatment and possibly die. This will have a great influence on the treatment decisions she makes. The risk of contra-lateral breast cancer in women with BRCA1 or 2 mutations is approximately 40% at 10 years versus 5–10% in sporadic cases 13 . Similarly, their risk of ovarian cancer will be increased. These factors will also have an impact on treatment planning and decisions. In addition, genetic counselling is relevant with regard to young children the patient may have or wish to have. In the UK the Human and Fertilisation and Embryology Authority has recently ruled that preimplantation genetic diagnosis will be allowed for women with BRCA1 or BRCA2 mutations. Currently, there are limited choices for risk reduction in young high-risk women, but these include chemoprevention with tamoxifen 14 and surgery, either mastectomy or bilateral salpingo-oophorectomy.
Surveillance for local recurrence and contra-lateral cancers Guidelines vary as to the optimal period of followup, but all recommend regular mammographic screening and caution against intensive follow-up with blood tests and bone scans, etc. However, the sensitivity of mammography in women under 40 is low due to the increased parenchymal density of the young breast. Only about 45% of young women will have had their cancer diagnosed by mammography, the mammogram being reported as either normal or benign in the remainder 15 . There is evidence that young age is an independent risk factor for local recurrence 16 and the risk of contralateral breast cancer is about 0.6% per year, but is increased greatly in BRCA carriers. Younger women therefore need close surveillance, but the optimal tool for screening for local recurrence and contra-lateral cancers has yet to be determined. Digital mammography has been shown to be more accurate in the young and dense breast 17 . Breast ultrasound is the imaging modality of choice in symptomatic women under 35 years, but it is not recommended as a screening tool and its role in breast cancer surveillance to complement
N. Roche mammography in young women has not been evaluated. MRI is increasingly used in screening highrisk women and it is also useful in distinguishing scarring from recurrence when mammography and ultrasound have been indeterminate 18,19 .
Fertility and future pregnancy Increasing numbers of women are delaying childbirth till their late 30s or early 40s; therefore, the potential loss of fertility as a result of treatment may contribute greatly to the emotional distress of a breast cancer diagnosis. Adjuvant therapies that may affect fertility are chemotherapy, tamoxifen and ovarian ablation. Tamoxifen in itself does not directly cause infertility, but women are advised not to get pregnant while taking tamoxifen. Fertility declines with age and currently we advise women to take tamoxifen for five years. The risk of infertility with chemotherapy will depend on the patient’s age and her ovarian reserve as well as the chemotherapy regime. Most data on chemotherapyrelated amenorrhea (CRA) comes from women having CMF 20 ; the rates of amenorrhea with anthracycline-based regimes are lower. In a series from MD Anderson, none of the patients under 30 developed CRA whereas rates of 33% were reported in women in their 30s 21 . There are limited data on newer agents such as taxanes, although they may incur higher rates of CRA. The return of menstruation following chemotherapy does not equate with fertility and there is evidence that ovarian reserve is depleted despite continued menstruation during chemotherapy 22 . Similarly, even if a woman continues to menstruate during chemotherapy, she is still likely to experience a premature menopause. There is some evidence that medically shutting down the ovaries during chemotherapy with goserelin may preserve fertility 23 , but research to validate this is still on-going. There are very little data to adequately inform women of the potential risks of undergoing fertility treatment either after treatment for breast cancer or at the time of diagnosis and before adjuvant systemic therapy starts. In the latter situation or in women who have become infertile following treatment there are three options to consider: cryopreservation of embryos, oocytes or ovarian tissue. Embryo cryopreservation requires a partner and both oocyte and ovarian tissue cryopreservation are still very much experimental, with only a few successful case reports 24,25 . Embryo cryopreservation requires ovarian hyperstimulation, which is pharmacologically induced
Follow-up after treatment for breast cancer in young women by causing an oestradiol surge. In attempts to avoid this surge in breast cancer patients naturalcycle IVF has been used, but the embryo yield is very low. Recently, tamoxifen and letrozole have been used in conjunction with FSH for ovarian stimulation and it has been demonstrated that embryo yield is as good as conventional FSH stimulation in non-cancer patients with significantly lower oestradiol peaks 26 . Current advice with regard to future pregnancy following breast cancer treatment is to wait at least two years. Results mainly from retrospective studies indicate that there is no significantly increased risk of recurrence as a result of future pregnancies 27 . As indicated above, little data exist on which to base advice for women on the risks of fertility treatment and future pregnancy, so it is vital that the multi-disciplinary team looking after young women facing the prospect of unwanted infertility have access to expert advice from fertility specialists dealing with breast cancer patients.
Hot flushes Hot flushes are experienced by more than 50% of menopausal women. The majority of young breast cancer patients will receive chemotherapy and therefore are at risk of a premature menopause. In addition, tamoxifen and ovarian ablation will cause hot flushes. Hot flushes are a major cause of morbidity in breast cancer patients and along with other menopause and treatment-related symptoms, they may make a young patient “feel old before her time” 28 . The symptoms are often considerably worse than those following a natural menopause 29 . Oestrogen replacement in the form of hormone replacement therapy (HRT) is the best way of treating the vasomotor symptoms, but its safety in breast cancer patients is unknown. Three trials were set up to address this question, one in the UK and two in Sweden, the HABITS trial and the Stockholm trial. The HABITS trial was terminated early as there was an increased number of recurrences in breast cancer patients on HRT compared with controls. This was not demonstrated in the Stockholm study, but it, like the UK study, was closed due the results of the HABITS trial 30 . Uncertainty therefore remains about the safety of HRT in breast cancer patients and its use is generally not recommended. Many alternatives are used and include relaxation techniques, acupuncture, herbs, isoflavones, medroxyprogesterone, megestrol acetate and nonhormonal medicines such as clonidine, gabapentin
S73
and venlafaxine, but there is little evidence to support their efficacy in many instances. As with HRT there are safety concerns with most alternatives. A recent systematic review and meta-analysis on the use of non-hormonal therapies concluded that there was some evidence to support the use of paroxetine, venlafaxine and gabapentin, but the adverse effects restrict the use in many women 31 . There is also a safety issue with the selective serotonin uptake inhibitors as they may interfere with tamoxifen metabolism 32 . The meta-analysis failed to find evidence to support the use of isoflavones 31 . Likewise, there are safety concerns with regard to their use in breast cancer patients 33 . The use of acupuncture has been shown to reduce the number of hot flushes, but the benefits are not usually sustained 34,35 , although the use of self-acupuncture after initial treatment has been reported to provide symptom control for prolonged periods 36 . Unfortunately, there is no well-tolerated, safe and efficacious treatment for the management of hot flushes. Young women will need advice about the different preparations. HRT provides the best relief of symptoms whereas consistent evidence for the use of herbs and isoflavones is lacking 31,37,38 . The use of progestogens and non-hormonal preparations listed above is often restricted by additional unpleasant side effects. The potential benefits in terms of quality of life need to be weighed up against the unquantifiable risk of a taking something that may precipitate disease recurrence. Relaxation techniques and acupuncture, which are entirely safe, do appear to have some benefits, but further evaluation is needed 36-39 .
Premature menopause As well as hot flushes, many women will experience and suffer other symptoms and consequences of therapy-induced menopause such as osteoporosis, lack of libido, vaginal dryness, mood swings, lack of concentration and short-term memory loss. These side effects are often worse in young women than in post-menopausal women having the same treatment 40 . Bone mineral density should be monitored in young women who have experienced a premature menopause and algorithms can be used to guide management 41 . Testosterone has been used to treat lack of libido, but long-term safety data are unknown 42 . Topical oestrogens are effective in relieving symptoms of vaginal atrophy, but again safety data in hormone-sensitive breast cancer patients are lacking. Systemic absorption is unpredictable and if a patient is taking an aromatase
S74 inhibitor there are theoretical concerns that raised oestrogen levels may abolish any beneficial effects of the aromatase inhibitor. Some women find non-hormonal vaginal lubricants helpful. As with the management of hot flushes, young women need to be given information about options for improving symptoms and the theoretical risks need to be balanced against quality of life issues. Protecting themselves against cancer recurrence is a major goal for most women and often they chose to tolerate symptoms rather than take something that is perceived to potentially increase the risk of recurrence 43 .
Psychosocial problems Body image and sexuality fears such as weight gain, hair loss and disfigurement are common to all women with breast cancer, but younger women are at greater risk of anxiety, depression and reduced quality of life. Women under the age of 35 comprise only 5% of breast cancer cases. A sense of isolation is therefore a key issue for many of these young women. They often feel cheated of a planned future and there may be a sense of loss or anger. If they have young children there is a fear that they will not see them grow up 44 . Fatigue is a very common symptom following breast cancer treatment and this can lead to difficulties in returning to work and possible financial problems. Those women who do not have jobs are still the primary home-maker and carer for the children. Depression can develop as a result of feeling inadequate or being unable to carry out this role as well as prior to the diagnosis and treatment for breast cancer. Healthcare professionals need to be alert to signs and symptoms of depression so that escalation into a major depressive illness can be prevented. Patients should be referred for counselling or psychiatric support where needed. Often the most valued intervention in dealing with the fear and isolation experienced by young women is access to peer support groups 44 .
Conclusions Only a small proportion of the many women under follow-up for breast cancer are women who were diagnosed and treated in their 20s or 30s. These young women, nonetheless, have a number of particular issues that need to be addressed in follow-up clinics. It has been shown that doctors are not particularly good at eliciting symptoms related to treatment morbidity 45 . Rather than concentrating solely on detecting cancer recurrence, clinicians need to be more susceptive
N. Roche to symptoms related to treatment morbidity and to the information needs of their patients. Endocrine symptom check-lists and psychological assessments should be carried out at consultations as appropriate. Large numbers of young women who are living with breast cancer and the menopause use complementary and alternative medicine in order to enhance survival and treat symptoms. They need access to evidence-based information to improve outcome and quality of life. Menopause and fertility questions are highly rated by patients, particularly in the follow-up period 46 . Fertility issues, despite being highly rated, are often not discussed or trivialised by health professionals 44,46 . These women should be managed by an extended multi-disciplinary team that includes genetics counsellors, fertility experts, psychologists and social workers. They should also all have access to support groups specific to young women.
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