The American Journal of Medicine
Volume 118, Issue 12, Supplement 2 , Pages 136-141, 19 December 2005

Breast cancer, menopause, and long-term survivorship: critical issues for the 21st century

  • Patricia A. Ganz, MD

      Affiliations

    • Corresponding Author InformationRequests for reprints should be addressed to Patricia A. Ganz, MD, Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Center, 650 Charles Young Drive South, Room A2-125 CHS, Los Angeles, California 90095-6900.

Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Center, UCLA Schools of Medicine and Public Health, University of California–Los Angeles, Los Angeles, California, USA

Article Outline

Breast cancer accounts for 33% of all incident cancers in women in North America, and there are an estimated >2 million breast cancer survivors in the United States today. Ovarian hormones are intimately involved in the initiation and promotion of breast cancer development, with targeted endocrine therapies being the most widely used as anticancer treatment. It is not surprising that these treatments frequently cause persistent menopausal symptoms in breast cancer survivors. In addition, adjuvant chemotherapy often induces premature menopause in younger patients with breast cancer. Some women at high risk for the development of breast cancer (e.g., precancerous breast disease, carriers of deleterious hereditary predisposition genes) experience vasomotor symptoms as a result of tamoxifen therapy or preventive oophorectomy. Clinical management of menopausal symptoms in these settings is complicated by the relative prohibition of hormonal therapies and the fact that breast cancer–directed therapies often exacerbate these menopausal symptoms. Thus, this special population of women requires unique management strategies and deserves separate consideration.

Keywords:  Breast cancer , Chemotherapy , Premature menopause , Vaginal dryness , Vasomotor symptoms

 

Survivors of breast cancer are a special population of concern in relation to the menopause. Breast cancer and the menopause frequently converge because of the increasing risk of this cancer during the early postmenopausal years. In addition, many premenopausal and perimenopausal women with breast cancer are at increased risk for earlier menopause because of the frequent use of adjuvant chemotherapy as a primary cancer treatment. 1, 2, 3, 4 As a consequence, management of menopausal symptoms is an important part of the follow-up healthcare for breast cancer survivors. 5 However, clinical management of menopausal symptoms in this setting is complicated by the relative prohibition of hormonal therapies as well as the fact that breast cancer–directed therapies often exacerbate these menopausal symptoms because hormonal antagonists are a central component of anticancer therapy. Therefore, this special population of patients requires unique management strategies.

The sections that follow review the epidemiology of breast cancer, the relation between breast cancer treatments and the menopause, the range and severity of menopause-related symptoms and conditions experienced by breast cancer survivors, as well as relevant menopause management strategies in this setting. A related special population is women who are at risk for hereditary breast cancer through inheritance of a deleterious mutation in the susceptibility gene BRCA1 or BRCA2. 6 Cancer-preventive strategies in these women also may cause menopausal symptoms.

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Epidemiology of breast cancer 

Breast cancer accounts for almost 33% of all incident cases of cancer in women, with >215,000 cases expected in 2005. 7 In Western industrialized countries, there are 2 peaks in incidence—in the 5th decade and in the 8th decade of life. These 2 peaks reflect lifetime exposure to endogenous sex steroid hormones, with the first peak influenced primarily by ovarian hormones and reproductive history (i.e., menarche, age at first pregnancy or nulliparity, lactation) 8, 9 and the second influenced by extraovarian sources of estrogens (e.g., androgens that are converted to estrogens via aromatization) as well by use of postmenopausal hormone therapy (HT). 10, 11 Observations from the epidemiologic literature strongly support the influence of endogenous hormonal exposure on breast density and bone density, suggesting that the latter are surrogate markers for tissue responsiveness in individual women, 12 reflecting the range of benefits (good bone health) and risks (increased breast tissue proliferative activity) of this exposure. The vast majority of women who develop breast cancer (∼75%) have no familial or hereditary/genetic risk for breast cancer, but their tissue response to endogenous hormones is likely controlled by a variety of genes involved in estrogen metabolism or tissue response. 13 In addition, reproductive, behavioral, and lifestyle factors interact with the genetic substrate of the woman to influence the development of breast cancer. Even the small number of women at high risk of developing breast cancer secondary to inheritance of a deleterious mutation in the susceptibility gene BRCA1 or BRCA2 may have their risk influenced by the same environmental exposures as do noncarriers. 14 Thus, hormonal exposures across the lifetime are intricately involved in the pathogenesis (initiation and promotion) of breast cancer from precancerous proliferative changes to noninvasive and invasive lesions.

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Breast cancer treatments 

Given the critical role of reproductive hormones in the initiation and promotion of breast cancer, it is not surprising that targeted endocrine therapies are the cornerstone of breast cancer treatment, whether in the preventive, adjuvant, or metastatic disease setting. 15, 16 Breast cancer tissue is tested at diagnosis for the presence or absence of estrogen and progesterone receptors, and women whose tumors contain these receptors (about 75% of cases) receive adjuvant endocrine therapy with tamoxifen or an aromatase inhibitor for ≥5 years. 17, 18 Evidence from randomized clinical trials provides excellent clinical guidance on the selection of endocrine therapy, with the choice of agent usually determined by the hormonal milieu of the woman at the time of treatment (i.e., premenopausal, perimenopausal, or postmenopausal). For example, aromatase inhibitors are prescribed only in postmenopausal women, whereas tamoxifen may be used in all women with breast cancer independent of menopausal status at diagnosis. There also is renewed interested in ovariectomy and ovarian suppression therapy in the adjuvant treatment of premenopausal women with breast cancer. 19

Chemotherapy is widely used as adjuvant therapy in women with tumors that are >1 cm in size, irrespective of age and tumor hormone receptor status. 3 In premenopausal or perimenopausal women, chemotherapy accelerates the menopausal transition and may lead to premature menopause. 4, 20 The efficacy of chemotherapy in this setting may be related to its ovarian-ablative properties because younger women who continue to menstruate after chemotherapy appear to have a poorer prognosis. 19 As a result, gonadotropin-releasing hormone agents are being studied in this setting. Thus, amenorrhea, whether transient or permanent, will likely continue to be a focus of treatment in premenopausal women with breast cancer.

Although there has been diminished use of postmenopausal HT since the publication of results from the Women’s Health Initiative (WHI) Hormone Trials, 21, 22 some women diagnosed with breast cancer are still taking HT at the time of diagnosis; these postmenopausal women usually have their HT abruptly terminated at the time of their breast cancer diagnosis. Menopausal symptoms can be quite troubling in this setting, with exacerbation if adjuvant endocrine therapy with tamoxifen or an aromatase inhibitor is initiated at the same time. This group of women often experience clinically significant vasomotor symptoms.

New developments in understanding the molecular characteristics of breast tumors (e.g., gene-expression profiles) are likely to lead to a focus on endocrine therapy alone as the primary treatment. 23, 24 Recently, a genetic risk classifier was validated that identifies approximately 50% of all estrogen receptor–positive tumors as being at low risk for recurrence when women are treated with adjuvant tamoxifen alone. 24 It is too early to know whether these results will be widely accepted; but if they are, many women will receive endocrine therapy alone, and this may spare some women from the side effects of chemotherapy-induced amenorrhea and menopausal symptoms.

Consequences of breast cancer treatments 

The widespread use of adjuvant therapy for breast cancer has led to dramatic improvements in survival. However, the price of this successful therapy is a range of short- and long-term health consequences, including premature menopause, infertility, vasomotor symptoms, vaginal dryness, dyspareunia, weight gain, and osteoporosis. 1, 20, 25, 26, 27, 28 In a cross-sectional study of >1,000 survivors of breast cancer 1 to 5 years after diagnosis (average 3 years), Ganz and colleagues 29 noted significantly increased rates of hot flashes, night sweats, vaginal dryness, vaginal discharge, and dyspareunia in women who had received any adjuvant therapy, with the highest rates among women who received both chemotherapy and tamoxifen (Figure 1, Figure 2). In another cross-sectional sample of >800 breast cancer survivors, chemotherapy led to vaginal dryness in both premenopausal and postmenopausal women, with sexual dysfunction most pronounced in younger women who developed amenorrhea. 30 Unfortunately, population norms determined with the same instrument are not available.

  • View full-size image.
  • Figure 1. 

    Percentage of breast cancer survivors (n = 1, 098) reporting hot flashes, night sweats, and vaginal discharge according to type of adjuvant therapy (Rx), assessed about 3 years after diagnosis. All statistical comparisons were adjusted for age and time since diagnosis, and all tests were done using likelihood ratio χ2 tests based on logistic regressions with and without treatment indicators. Frequencies presented are unadjusted for age and time since diagnosis. *For all values, P <0.0001. Chem = chemotherapy; Tam = tamoxifen. (Adapted from Recent Results Cancer Res.29)

  • View full-size image.
  • Figure 2. 

    Percentage of breast cancer survivors (n = 1, 098) reporting vaginal dryness, dyspareunia, and weight gain according to type of adjuvant therapy (Rx), assessed about 3 years after diagnosis. All statistical comparisons were adjusted for age and time since diagnosis, and all tests were done using likelihood ratio χ2 tests based on logistic regressions with and without treatment indicators. Frequencies presented are unadjusted for age and time since diagnosis. *For all values, P <0.01. Chem = chemotherapy; Tam = tamoxifen. (Adapted from Recent Results Cancer Res.29)

In a study focused specifically on the reproductive and late health effects of breast cancer in younger women, Ganz and colleagues 20 recruited 577 survivors of breast cancer (diagnosed 2 to 10 years earlier) from 2 hospital tumor registries to participate in a mailed survey. All women were aged ≤50 years at the time of diagnosis and were surveyed approximately 6 years after diagnosis. Although overall health-related quality of life was good for these survivors, women who were the youngest at diagnosis (25 to 34 years of age) experienced the most subsequent difficulties in the emotional, social, and energy domains of quality of life. 20 Women in all age groups experienced frequent hot flashes, night sweats, vaginal dryness, and dyspareunia, and these increased in frequency with age. Amenorrhea occurred frequently in women who were ≥40 years of age at diagnosis, and treatment-associated menopause was associated with poorer self-perceived health. 20 Having had a menopausal transition during breast cancer treatment was associated with worse hot flash severity, independent of current menopausal status. 31

Vaginal dryness is a significant problem for aging women independent of a breast cancer diagnosis. 32 After breast cancer, however, new onset of menopause, use of chemotherapy, or withdrawal of HT can exacerbate this problem. In 1 study, vaginal dryness was associated with an increased risk for sexual dysfunction in survivors of breast cancer. 33 Therefore, attention to this problem is important for the sexual health and rehabilitation of women who survive breast cancer.

There is no accurate population estimate for the number of survivors of breast cancer who have menopause-associated problems. However, given the frequency of vasomotor symptoms and vaginal dryness noted in various samples of breast cancer survivors or those who received preventive therapies for breast cancer, 20, 29, 30, 34, 35 the numbers of women in this special population are expected to expand during the next decade. In particular, the substantial proscription against the use of HT in these women limits the management strategies for these symptoms, and women are often reluctant to consider HT options that may be considered in women without a history of breast cancer. Therefore, a substantial number of women in this special population have uncontrolled menopause-associated symptoms.

Management of menopause-related symptoms in survivors of breast cancer 

During the last decade, there have been many studies designed to test non-HT strategies for management of menopausal symptoms in survivors of breast cancer 36, 37, 38, 39, 40, 41 (see other articles in this supplement 42, 43, 44), reflecting the prevalence and severity of hot flashes, night sweats, and vaginal dryness observed clinically in these women. Nevertheless, in a study we conducted recently with breast cancer survivors experiencing severe menopausal symptoms (e.g., hot flashes, vaginal dryness, urinary incontinence), recruitment was challenging because women were often reluctant to consider taking medication for their symptoms. 36 This was also found in an interview study that we performed with older breast cancer survivors. 45 In clinical practice, breast cancer survivors will often forgo the use of medication for vasomotor symptoms, but they are more often willing to try something to alleviate vaginal dryness, especially if they are sexually active. In our clinical trial of managing menopausal symptoms, a vaginal moisturizer, used as part of the intervention program, alleviated symptoms and improved sexual functioning. 36 Vaginal dryness is less transient than vasomotor symptoms, and it may worsen over time. As a result, there has been some acceptance in the oncologic community (especially in the prevention setting), for allowing the use of low-dose vaginal estrogen preparations that do not raise serum estradiol levels above postmenopausal levels. 46, 47 However, there is clearly some potential risk with such therapy since the current use of aromatase inhibitor treatment as systemic endocrine therapy is aimed at reducing serum estradiol levels to very low levels, and thus it may be considered counterintuitive to permit even low levels of estrogen therapy for relief of vaginal symptoms. Nevertheless, breast cancer survivors who have significant urogenital symptoms that are not relieved by nonhormonal preparations may want to consider this option.

Another complaint that is common among breast cancer survivors is loss of sexual desire. This can be complicated to assess and may be multifactorial in etiology (e.g., associated with fatigue, depression, partner problems), but it may also be caused by low testosterone levels. This is sometimes a late effect of chemotherapy-induced ovarian failure or ovariectomy. 48, 49 For some women, low-dose testosterone therapy may be of benefit; however, use in breast cancer survivors and women at high risk is controversial in that endogenous testosterone levels are associated with an increased risk of breast cancer. 50, 51 If prescribed, low-dose testosterone may be applied sparingly as a cream or gel. 52

Before the results of the WHI, 21, 22 HT was widely advocated for healthy postmenopausal women for symptom relief and chronic disease prevention (e.g., heart disease, osteoporosis, dementia). Although some observational studies suggested that HT was safe in breast cancer survivors, 53 there was much skepticism about this in survivors or patients with breast cancer, among both physicians and patients. 45 Recently, a randomized controlled trial of HT after breast cancer (the HABITS [Hormonal Replacement Therapy After Breast Cancer—Is It Safe?] trial) was terminated early because of an increase in adverse events in the women treated with HT. 54 After a median follow-up of 2.1 years, 26 patients in the HT group and 7 patients in the non-HT group had a new breast cancer event, and these results were considered sufficiently serious to abandon further study of HT in patients with breast cancer. The WHI results in healthy women make it clear that there is limited benefit from HT beyond symptom relief, and with the finding of the HABITS trial now showing that there may be serious risks for breast cancer recurrence with such therapy, there is no justification of HT over the long term in women with breast cancer unless all other therapies have been exhausted and the patient is fully informed about the potential risks.

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Women at risk for hereditary breast–ovarian cancer syndrome 

About 5% to 10% of breast cancer cases can be attributed to the presence of an inherited deleterious mutation in a gene that predisposes to the development of breast cancer (i.e., BRCA1 or BRCA2). Increasingly, clinical testing for these mutations is being considered in women who come from families with multiple cases of breast or ovarian cancer or when breast cancer has occurred at a particularly young age (e.g., <40 years). For those women who are unaffected by cancer as yet, knowledge of the presence of a deleterious mutation may prompt preventive decisions that range from more intensive surveillance and screening 55 to use of chemopreventive agents 56 or to surgical preventive interventions such as ovariectomy or mastectomy. 57 Many women with BRCA1 or BRCA2 mutations, with and without breast cancer, who have completed their families will choose a strategy of bilateral ovariectomy (usually with hysterectomy and fallopian tube removal) to reduce their risk of ovarian cancer and breast cancer. 6, 58, 59 In this setting, vasomotor symptoms are extremely severe acutely, and most clinicians caring for these women offer HT for a period. In 1 study that evaluated symptoms and quality of life approximately 2 years after risk-reducing ovarian surgery, 60 only a small number of women were taking HT, and vaginal dryness and dyspareunia were the most significant symptoms reported (about 25% to 30% incidence). In this study sample, quality of life and depressive symptoms were comparable to those in the general population. However, these results are limited by the fact that most women had a diagnosis of breast cancer in the past (83%) and <25% were premenopausal or perimenopausal at the time of surgery. 60 In unaffected women who are substantially younger when this surgery is done, some experts recommend HT until the age of 50 years, the approximate time when natural menopause would otherwise occur. 57

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Questions for future research 

In conclusion, with >200,000 new cases of breast cancer per year and 5-year survival rates >85%, increases in the absolute number of survivors of breast cancer can be expected in the decades to come. Menopause-associated symptoms in this target population will be complicated by an even longer duration of cancer-directed endocrine therapy 17 as well as by an increased use of ovarian-suppression therapy in premenopausal women. In addition, more women will be taking endocrine-directed treatments for prevention of breast cancer in the future. Important research questions therefore include the following: (1) How can we reconcile the survival benefits of breast cancer therapies, many of which induce menopausal symptoms, with their potential for decrements in aspects of quality of life and health of women across a broad age span? Alternatively, are the menopausal symptoms induced by treatment worse than the threat of cancer in some women? (2) Can we find better methods of managing menopausal symptoms in breast cancer survivors and women at high risk for the disease who are receiving anticancer therapy? (3) Are there any “safe” forms of HT that can be used for short periods in breast cancer survivors that will not increase the risk of recurrent cancer? Although these research questions have particular salience for women with a history of breast cancer, answers to these questions can also assist all women who may be experiencing menopausal symptoms and who are weighing the risks and benefits of HT.

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References 

  1. Ganz PA . Menopause and breast cancer (symptoms, late effects, and their management) . Semin Oncol . 2001;28:274–283
  2. Partridge AH , Burstein HJ , Winer EP . Side effects of chemotherapy and combined chemohormonal therapy in women with early-stage breast cancer . [published correction appears in J Natl Cancer Inst. 2002;94:866 and J Natl Cancer Inst Monogr. 2003;(31):131] J Natl Cancer Inst Monogr . 2001;30:135–142
  3. National Institutes of Health Consensus Development Panel . National Institutes of Health Consensus Development Conference statement (adjuvant therapy for breast cancer, November 1–3, 2000) . J Natl Cancer Inst . 2001;30:5–15
  4. Goodwin PJ , Ennis M , Pritchard KI , Trudeau M , Hood N . Risk of menopause during the first year after breast cancer diagnosis . J Clin Oncol . 1999;17:2365–2370
  5. Burstein HJ , Winer EP . Primary care for survivors of breast cancer . N Engl J Med . 2000;343:1086–1094
  6. Narod SA , Offit K . Prevention and management of hereditary breast cancer . J Clin Oncol . 2005;23:1656–1663
  7. Jemal A , Murray T , Ward E , et al.   Cancer statistics, 2005 . CA Cancer J Clin . 2005;55:10–30
  8. Dickson RB , Russo J . Biochemical control of breast development . In:  Harris JR ,  Lippman ME ,  Morrow M ,  Osborne CK editor. Diseases of the Breast . Philadelphia: Lippincott Williams & Wilkins; 2000;p. 15–31
  9. Russo J , Russo IH . Genotoxicity of steroidal estrogens . Trends Endocrinol Metab . 2004;15:211–214
  10. Colditz GA . Postmenopausal estrogens and breast cancer . J Soc Gynecol Investig . 1996;3:50–56
  11. Schairer C . Progesterone receptors—animal models and cell signalling in breast cancer (implications for breast cancer of inclusion of progestins in hormone replacement therapies) . Breast Cancer Res . 2002;4:244–248
  12. Clemons M , Goss P . Estrogen and the risk of breast cancer . N Engl J Med . 2001;344:276–285
  13. Hankinson SE , Colditz GA , Willett WC . Towards an integrated model for breast cancer etiology (the lifelong interplay of genes, lifestyle, and hormones) . Breast Cancer Res . 2004;6:213–218
  14. King MC , Marks JH , Mandell JB . Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2 . Science . 2003;302:643–646
  15. Early Breast Cancer Trialists’ Collaborative Group . Tamoxifen for early breast cancer . Cochrane Database Syst Rev . 2001;1:CD000486
  16. Alberg AJ , Lam AP , Helzlsouer KJ . Epidemiology, prevention, and early detection of breast cancer . Curr Opin Oncol . 1999;11:435–441
  17. Goss PE , Ingle JN , Martino S , et al.   A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer . N Engl J Med . 2003;349:1793–1802
  18. Winer EP , Hudis C , Burstein HJ , et al.   American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer (status report 2004) . J Clin Oncol . 2005;23:619–629
  19. Castiglione-Gertsch M , O’Neill A , Price KN , et al.  International Breast Cancer Study Group   Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer (a randomized trial) . J Natl Cancer Inst . 2003;95:1833–1846
  20. Ganz PA , Greendale GA , Petersen L , Kahn B , Bower JE . Breast cancer in younger women (reproductive and late health effects of treatment) . J Clin Oncol . 2003;21:4184–4193
  21. Rossouw JE , Anderson GL , Prentice RL , et al.  Writing Group for the Women’s Health Initiative Investigators   Risks and benefits of estrogen plus progestin in healthy postmenopausal women (principal results from the Women’s Health Initiative randomized controlled trial) . JAMA . 2002;288:321–333
  22. Anderson GL , Limacher M , Assaf AR , et al.   Effects of conjugated equine estrogen in postmenopausal women with hysterectomy (the Women’s Health Initiative randomized controlled trial) . JAMA . 2004;291:1701–1712
  23. van de Vijver MJ , He YD , ’t Veer LJ , et al.   A gene-expression signature as a predictor of survival in breast cancer . N Engl J Med . 2002;347:1999–2009
  24. Paik S , Shak S , Tang G , et al.   A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer . N Engl J Med . 2004;351:2817–2826
  25. Ganz PA , Greendale GA . Menopause and breast cancer (addressing the secondary health effects of adjuvant chemotherapy) . J Clin Oncol . 2001;19:3303–3305
  26. Ganz PA . Impact of tamoxifen adjuvant therapy on symptoms, functioning, and quality of life . J Natl Cancer Inst Monogr . 2001;30:130–134
  27. Greendale GA , Petersen L , Zibecchi L , Ganz PA . Factors related to sexual function in postmenopausal women with a history of breast cancer . Menopause . 2001;8:111–119
  28. Meyerowitz BE , Desmond KA , Rowland JH , Wyatt GE , Ganz PA . Sexuality following breast cancer . J Sex Marital Ther . 1999;25:237–250
  29. Ganz PA , Rowland JH , Meyerowitz BE , Desmond KA . Impact of different adjuvant therapy strategies on quality of life in breast cancer survivors . Recent Results Cancer Res . 1998;152:396–411
  30. Ganz PA , Rowland JH , Desmond K , Meyerowitz BE , Wyatt GE . Life after breast cancer (understanding women’s health-related quality of life and sexual functioning) . J Clin Oncol . 1998;16:501–514
  31. Crandall C , Petersen L , Ganz PA , Greendale GA . Association of breast cancer and its therapy with menopause-related symptoms . Menopause . 2004;11:519–530
  32. Avis NE , Stellato R , Crawford S , Johannes C , Loncope C . Is there an association between menopause status and sexual functioning? . Menopause . 2000;7:297–309
  33. Ganz PA , Desmond KA , Belin TR , Meyerowitz BE , Rowland JH . Predictors of sexual health in women after a breast cancer diagnosis . J Clin Oncol . 1999;17:2371–2380
  34. Ganz PA , Kwan L , Stanton AL , et al.   Quality of life at the end of primary treatment of breast cancer (first results from the moving beyond cancer randomized trial) . J Natl Cancer Inst . 2004;96:376–387
  35. Day R , Ganz PA , Costantino JP , Cronin WM , Wickerham DL , Fisher B . Health-related quality of life and tamoxifen in breast cancer prevention (a report from the National Surgical Adjuvant Breast and Bowel Project P-1 Study) . J Clin Oncol . 1999;17:2659–2669
  36. Ganz PA , Greendale GA , Petersen L , Zibecchi L , Kahn B , Belin TR . Managing menopausal symptoms in breast cancer survivors (results of a randomized controlled trial) . J Natl Cancer Inst . 2000;92:1054–1064
  37. Goldberg RM , Loprinzi CL , O’Fallon JR , et al.   Transdermal clonidine for ameliorating tamoxifen-induced hot flashes . J Clin Oncol . 1994;12:155–158
  38. Loprinzi CL , Michalak JC , Quella SK , et al.   Megestrol acetate for the prevention of hot flashes . N Engl J Med . 1994;331:347–352
  39. Barton DL , Loprinzi CL , Quella SK , et al.   Prospective evaluation of vitamin E for hot flashes in breast cancer survivors . J Clin Oncol . 1998;16:495–500
  40. Loprinzi CL , Abu-Ghazaleh S , Sloan JA , et al.   Phase III randomized double-blind study to evaluate the efficacy of a polycarbophil-based vaginal moisturizer in women with breast cancer . J Clin Oncol . 1997;15:969–973
  41. Loprinzi CL , Kugler JW , Sloan JA , et al.   Venlafaxine in management of hot flashes in survivors of breast cancer (a randomised controlled trial) . Lancet . 2000;356:2059–2063
  42. Loprinzi CL , Stearns V , Barton D . Centrally active menopausal hot flash therapies . Am J Med . 2005;118(suppl 12B):118S–123S
  43. Carpenter JS , Neal JG . Other complementary and alternative medicine modalities (acupuncture, magnets, reflexology, and homeopathy) . Am J Med . 2005;118(suppl 12B):109S–117S
  44. Low Dog T . Menopause (a review of botanical dietary supplements) . Am J Med . 2005;118(suppl 12B):98S–108S
  45. Ganz PA , Greendale GA , Kahn B , O’Leary JF , Desmond KA . Are older breast carcinoma survivors willing to take hormone replacement therapy? . Cancer . 1999;86:814–820
  46. Ballagh SA . Vaginal rings for menopausal symptom relief . Drugs Aging . 2004;21:757–766
  47. Suckling J , Lethaby A , Kennedy R . Local oestrogen for vaginal atrophy in postmenopausal women . Cochrane Database Syst Rev . 2003;4:CD001500
  48. Sherwin BB . Changes in sexual behavior as a function of plasma sex steroid levels in post-menopausal women . Maturitas . 1985;7:225–233
  49. Sherwin BB , Gelfand MM . The role of androgen in the maintenance of sexual functioning in oophorectomized women . Psychosom Med . 1987;49:397–409
  50. Berrino F , Muti P , Micheli A , et al.   Serum sex hormone levels after menopause and subsequent breast cancer . J Natl Cancer Inst . 1996;88:291–296
  51. Key T , Appleby P , Barnes I , et al.  Endogenous Hormones and Breast Cancer Collaborative Group   Endogenous sex hormones and breast cancer in postmenopausal women (reanalysis of nine prospective studies) . J Natl Cancer Inst . 2002;94:606–616
  52. Goldstat R , Briganti E , Tran J , Wolfe R , Davis SR . Transdermal testosterone therapy improves well-being, mood, and sexual function in premenopausal women . Menopause . 2003;10:390–398
  53. Col NF , Hirota LK , Orr RK , Erban JK , Wong JB , Lau J . Hormone replacement therapy after breast cancer (a systematic review and quantitative assessment of risk) . J Clin Oncol . 2001;19:2357–2363
  54. Holmberg PL , Anderson H . HABITS (hormonal replacement therapy after breast cancer—is it safe?), a randomised comparison (trial stopped) . Lancet . 2004;363:453–455
  55. Warner E , Plewes DB , Hill KA , et al.   Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination . JAMA . 2004;292(11):1317–1325
  56. King MC , Wieand S , Hale K , et al.   Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2 (National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial) . JAMA . 2001;286:2251–2256
  57. Wooster R , Weber BL . Breast and ovarian cancer . N Engl J Med . 2003;348:2339–2347
  58. Kauff ND , Satagopan JM , Robson ME , et al.   Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation . N Engl J Med . 2002;346:1609–1615
  59. Schwartz MD , Kaufman E , Peshkin BN , et al.   Bilateral prophylactic oophorectomy and ovarian cancer screening following BRCA1/BRCA2 mutation testing . J Clin Oncol . 2003;21:4034–4041
  60. Robson M , Hensley M , Barakat R , et al.   Quality of life in women at risk for ovarian cancer who have undergone risk-reducing oophorectomy . Gynecol Oncol . 2003;89:281–287

 The opinions offered at the National Institutes of Health (NIH) State-of-the Science Conference on Management of Menopause-Related Symptoms and published herein are not necessarily those of the National Institute on Aging (NIA) and the Office of Medical Applications of Research (OMAR) or any of the cosponsoring institutes, offices, or centers of the NIH. Although the NIA and OMAR organized this meeting, this article is not intended as a statement of Federal guidelines or policy.Publication of the online supplement was made possible by funding from the NIA and the National Center for Complementary and Alternative Medicine of the NIH, US Department of Health & Human Services.Supported in part by an American Cancer Society Clinical Research Professorship awarded to Dr. Ganz.

PII: S0002-9343(05)00905-8

doi:10.1016/j.amjmed.2005.09.047

The American Journal of Medicine
Volume 118, Issue 12, Supplement 2 , Pages 136-141, 19 December 2005

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