Clinical practice guidelines for the care and treatment of breast cancer:
9. Follow-up after treatment for breast cancer (2005 update)

Eva Grunfeld, Sukhbinder Dhesy-Thind, Mark Levine, for the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer*

Dr. Grunfeld is Professor of Medicine, Dalhousie University, and Director of Health Services and Outcomes Research, Cancer Care Nova Scotia, Halifax, NS. Dr. Dhesy-Thind is with the Cancer Care Ontario Juravinski Regional Cancer Centre and is Assistant Professor in the Department of Medicine, McMaster University, Hamilton, Ont. Dr. Levine is Professor in the Departments of Clinical Epidemiology and Biostatistics and of Medicine and is the Buffet Taylor Chair in Breast Cancer Research, McMaster University, Hamilton, Ont.

*The steering committee is part of Health Canada's Canadian Breast Cancer Initiative. (A list of members appears on page 17.)

The patient guide, containing questions and answers for women on follow-up care, has also been updated and is available at

See also: 


Objective: To provide information and recommendations to patients and their physicians regarding follow-up strategies and topics relevant to follow-up after treatment for breast cancer.

Evidence: Systematic review of the English-language literature retrieved from MEDLINE (1991 to January 2004). A nonsystematic review of the literature was continued through January 2005.


Validation: The original guideline was updated by a writing committee, which then submitted it for review, revision and approval by the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. The current update has been peer reviewed.

Sponsor: The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer was convened by Health Canada.

Completion Date: March 2005.

This guideline updates the previously published guideline on follow-up after treatment for breast cancer.1 The evidence on the goals of follow-up and the components of the follow-up program are updated. As well, special topics of concern to breast cancer survivors, such as cognitive functioning, fatigue, weight management, osteoporosis, sexual functioning and pregnancy, are discussed. These topics were not included in the original 1998 version of the guideline. The topics of hormone replacement therapy (see guideline 14) and lymphedema (see guideline 11) are presented elsewhere.


The evidence reviewed for this document was obtained through a systematic review of the English-language literature retrieved from MEDLINE (1991 to January 2004). Search terms included "breast neoplasms," "follow-up," "randomized controlled trials," "meta analysis," "quality of life," "fatigue," "weight gain," "osteoporosis," "sexuality" and "pregnancy." A nonsystematic review of the literature and monitoring of major conferences on breast cancer were continued through January 2005.

The quality of the evidence on which conclusions are based is categorized into 5 levels.2 The iterative process used to develop this guideline is described elsewhere.3 A writing committee updated the original guideline and submitted it to the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer for further review, revision and approval.

Recommendations (including evidence and rationale)

Goals of follow-up

Regular follow-up surveillance should aim to achieve 4 principal objectives:

1. To provide patients with support and counselling

Breast cancer survivors can experience a variety of physical and psychological symptoms during their follow-up. Certain types of early symptoms, such as soft-tissue swelling, hematomas, seromas of the breast area, and numbness or stiffness of the upper arm, are attributable to surgery. Later symptoms may be due to surgery (e.g., postmastectomy syndrome: see 2001 update of guideline 10 for the management of chronic pain after mastectomy); to irradiation (e.g., erythema, swelling, tenderness and skin edema: see 2003 update of guideline 6); to lymphedema (see guideline 11); or to menopausal symptoms associated with tamoxifen and induced by ovarian ablation or chemotherapy (see guideline 14).

Psychosocial problems are most pronounced during the first year after breast cancer diagnosis,4,5 whereas long-term psychosocial adjustment is generally excellent.6 Ganz and colleagues reported the results of a longitudinal cohort study involving 817 breast cancer survivors who were disease free.6 At an average of 6.3 years after diagnosis, physical well-being and emotional well-being were excellent, and the modest clinically nonsignificant changes in the physical domains of health-related quality of life (HRQL) were consistent with an aging population. The subgroup of women who had received systemic adjuvant therapy, however, had a decline in several aspects of physical functioning. This suggests that systemic therapy can be associated with long-term effects on quality of life. There were no differences in HRQL according to the type of primary breast cancer surgery, which is consistent with findings from other studies.7 A negative impact was found on work life and career in the study by Ganz and colleagues,6 which was also shown in a Canadian study.8 Ganz and associates also conducted a retrospective survey of the quality of life of 577 young (< 50 years of age at the time of diagnosis) breast cancer survivors.9 The patients were surveyed approximately 6 years after diagnosis. Overall, quality of life was good but was decreased in women less than 35 years of age, particularly those who underwent early menopause. Ganz and colleagues also reported the results of a survey of the quality of life of 691 women aged 65 years or more who were interviewed 3 and 15 months after breast cancer surgery.10 Quality of life decreased initially but improved over time. For women taking tamoxifen, extrapolation from a randomized trial of tamoxifen versus placebo for primary prevention of breast cancer suggests that tamoxifen does not increase the risk of depression (level I evidence).11

It is through follow-up visits that physical and psychological issues can be discussed, and treatment and reassurance provided, as required.

2. To detect potentially curable conditions such as local recurrence of cancer in the breast following breast-conserving surgery and new cancers in the opposite breast

In patients treated with breast-conserving surgery (BCS) and radiotherapy, local recurrence may develop in the same breast. The rate of local recurrence at 20 years of follow-up has been reported to be between 8.8% 12 and 14.3%.13 Local recurrence in the breast can often be detected earlier by mammographic examination14 than by physical examination and is potentially curable by mastectomy.15 Thus, after BCS, regular examination is recommended with the aim of detecting local recurrences early. However, recurrence in the breast early (i.e., within 1 or 2 years after surgery) is often an indicator of aggressive disease and systemic metastases.16,17 A local recurrence in the chest wall after mastectomy, however, often has the same prognostic significance as a distant metastasis, and its early detection and treatment are unlikely to influence survival.15

It is estimated that women who have had breast cancer are at 2 to 6 times greater risk of a new primary cancer in the contralateral breast than are women who have not had breast cancer.18 The absolute risk is between 0.5% and 1.0% per year.19 In one series, which involved breast cancer patients who subsequently had contralateral breast cancer, no difference in survival was detected between patients with unilateral versus bilateral cancers.20 In the case of bilateral breast cancer, prognosis is determined by whichever breast tumour has the worst prognosis. For early stage breast cancer, early detection of a contralateral breast cancer may be beneficial. There is no direct proof, however, that early detection will improve survival in these patients.

Regular mammographic screening of healthy populations results in earlier detection of breast cancer and reduced rates of death from breast cancer among women over 50 years of age.21 Therefore, by extrapolation, regular clinical and mammographic examinations of breast cancer patients after treatment constitute, in effect, screening of a high-risk population, and these measures could result in improved survival. However, any such benefit is likely to be small because of the small number of second cancers involved and the competing mortality related to the first cancer.

Nevertheless, early detection is facilitated when clinical and mammographic examinations have been carried out to establish a "baseline" after the inflammatory changes resulting from surgery and radiotherapy have subsided.

3. To provide care for patients in whom metastatic disease develop

Several observational studies,22,23,24 2 randomized controlled trials25,26 and 1 simulation study27 have shown that early detection of distant metastases does not improve survival (level I evidence). Symptoms often develop between visits, and physicians rarely detect abnormalities in asymptomatic patients.22 However, early treatment of metastases can sometimes influence morbidity; thus, with this objective in mind, patients should be encouraged to report new symptoms promptly.

4. To monitor outcome

Cancer specialists recognize that monitoring patient outcomes, such as survival, morbidity and quality of life, is an important aspect of determining the effectiveness of treatment.28 In order to compare treatment outcomes with national and international standards, such information must be collected systematically, completely and in a format that allows for regular analysis.

The follow-up program

There is no compelling evidence to support any particular frequency of visits. In a British study, women were randomly allocated either to a follow-up schedule of visits every 3 months in year 1, every 4 months in year 2 and every 6 months in years 3 to 5 or to a schedule of 1 visit every 1 or 2 years. No benefit was detected from the more frequent visits, and patients in both groups expressed a preference for reducing rather than increasing the number of follow-up visits (level II evidence).29 In another British study, patients were randomly allocated to receive standard clinic follow-up versus no routine follow-up. Patients in the latter group received written information on signs and symptoms of recurrence with instructions to make telephone contact with a nurse if they experienced any problems.30Although no differences were found in either HRQL or patient satisfaction outcomes, the study was conducted for 1 year only and no clinical outcomes were reported (level II evidence).

The frequency of visits requires a balancing of the probable health benefits against the inconvenience, stress and costs of frequent visits and the number of false-positive test results they may generate. Although follow-up visits can reassure patients, they can also cause anxiety and remind women of their disease without ever being able to provide complete reassurance that they are cured.31,32 In a report presented at the Bari Consensus Conference, Boccardo and colleagues suggested 4 visits per year for 2 years, 2 visits per year for the next 3 years and annual visits thereafter.33 The American Society of Clinical Oncology recommends visits every 3 to 6 months for the first 3 years, every 6 to 12 months for the next 2 years, then annually.34 In general, follow-up should be tailored to the individual needs of the patient.

Treatment with tamoxifen causes a small increase in the risk of endometrial cancer (level I evidence).35,36 The annual risk is approximately 2 per 1000 women and is higher among those over 50 years of age than among younger women. Most women taking tamoxifen in whom endometrial cancer develops will have vaginal bleeding.37 Thus, it is important to ask about vaginal bleeding during the history-taking.34 When such bleeding is present without an obvious cause, endometrial biopsy should be carried out. Screening with either transvaginal ultrasonography or endometrial sampling is not warranted because of the high false-positive rates and the low yield of clinically important results.38,39

Physical and mammographic examinations are complementary: findings on mammographic examination may be normal even when a palpable cancer is present, and nonpalpable cancers may be detected by mammographic examination.40,41,42 Although a systematic review of the literature demonstrated that the benefits of annual mammograms are based only on case series and observational studies,43annual mammograms are widely recommended in conjunction with regular physical examination.

In the absence of evidence that early treatment of metastatic disease will prolong life, one should avoid the inconvenience and expense of carrying out routine tests to detect it. In one trial, 655 patients who were randomly assigned to receive intensive surveillance consisting of physician visits, bone scanning, liver echographic examination, chest radiography and laboratory tests had an almost identical 6-year survival and HRQL to that of a control group of 665 women who received only tests that were clinically indicated (level I evidence).25 Both groups had annual mammographic examination of the contralateral breast. In another randomized trial of similar size and duration, chest radiographs and bone scans obtained every 6 months had no influence on mortality at 5 years.26 These results have been reaffirmed in a recent meta-analysis of these studies.44 Except for mammographic examination,43 scientific evidence does not support the routine use of any other instrumental or laboratory test, including biologic markers.33,34,45,46,47

Patients should understand clearly that the presence of persistent symptoms, such as bone pain, cough, breast lumps, mastectomy scar changes, fatigue and anorexia, should be reported without waiting for a scheduled visit.

Breast self-examination is not recommended as a screening manoeuvre for women without breast cancer.48 For women with breast cancer, evidence is lacking that breast self-examination can improve survival. In a follow-up study involving 1004 women newly diagnosed with breast cancer, the cancers found by those who practised self-examination were smaller and associated with fewer involved axillary lymph nodes.49 Thus, it is theoretically possible that earlier diagnosis may improve survival.

Psychosocial support has been defined as information, advice or tangible aid provided through contact with a social network that has beneficial effects for the recipient.50 Support can be given to patients by other breast cancer survivors.51 Randomized controlled trials evaluating the effect of different forms of psychosocial interventions on psychosocial outcomes of breast cancer survivors have had conflicting results: some found a positive effect on some psychosocial domains,52,53,54,55 whereas others found no effect.56

The effect of psychosocial interventions on survival is also uncertain. Although an early trial by Spiegel and colleagues showed longer survival among 86 patients with metastatic breast cancer randomly allocated to receive a psychosocial supportive intervention than among patients in the control group,57 a recent Canadian trial found no difference in survival between 235 women with metastatic breast cancer randomly assigned to a psychosocial support intervention and those in the control group (level I evidence).58

The results of these studies are difficult to interpret because of the many different patient groups, interventions and outcomes being studied. Nevertheless, in a review of the evidence, Fallowfield recommended that psychological interventions be placed "firmly on the list of requirements for good cancer care."59 Thus, psychosocial support, whether provided by health care workers, family, friends or organized support groups, should be facilitated and encouraged.

Improvement in the care of future patients with breast cancer depends on the participation of sufficient numbers of patients in clinical trials. Therefore, physicians treating patients with breast cancer should be aware of currently available trials, and patients should be given the opportunity to participate in them.

Although early follow-up visits are normally carried out by the specialist who has been responsible for treatment (the surgeon, the medical oncologist or the radiation oncologist), the responsibility for long-term follow-up care is frequently not defined. In an Italian study, one-third of 284 women complained of difficulties in follow-up owing to lack of cooperation and integration of follow-up procedures among specialists.60

The individuals or organizations that are the most appropriate for carrying out follow-up may differ according to the circumstances. In a British study, follow-up in a general practice was found to be acceptable to both patients and general practitioners.31 In this study, involving 296 women randomly allocated to receive follow-up care either in the hospital or in general practice, there was no significant difference between the 2 groups in time to confirmation of recurrence or in scores for social functioning, mental health or general health perception (level II evidence).61In Canada, continuing care is often carried out by specialists. In a study in southwestern Ontario, family physicians were involved in the care of only 17.5% of 183 women with stage I breast cancer.62 In another Canadian trial, 968 women with early stage breast cancer who had completed their primary treatment (e.g., chemotherapy or radiotherapy) were randomly allocated to receive follow-up by either their own family physician or an oncologist at a cancer centre.63At a median follow-up of 3.5 years, there was no difference between the 2 groups in the primary outcome of serious clinical events (3.3% in the family physician group and 3.7% in the cancer centre group; 0.4% difference; 95% confidence interval [CI] –2.02% to 2.83%).

In a paper presented at the Bari Consensus Conference, the authors concluded that, after long periods of care by their various oncologists, women may feel abandoned when discharged from their cancer clinic. They concluded that patients wanted a "team" of health care professionals to be accessible, when necessary, for their care and treatment.51Researchers in the United Kingdom have reached the same conclusions.64 Thus, when family physicians assume responsibility for follow-up, contact should be maintained with the treating specialists. When responsibility is transferred, irrespective of who is responsible for the follow-up surveillance, the patient must take part in the decision and be kept fully informed of the follow-up plans from the beginning to avoid any feelings of abandonment.

Not all of the health care professionals who have taken part in the diagnosis and management of a woman's breast cancer will necessarily wish to be kept informed of the patient's progress during follow-up. However, for those who do, clear arrangements for the transfer of follow-up information will make for improved care and avoid unnecessary repetition of tests.34

Special issues

Cognitive functioning

Breast cancer survivors often complain of memory problems, a phenomenon that has been called "chemobrain" or "chemofog."65 Phillips and Bernhard recently reviewed the literature on the effect of adjuvant chemotherapy on cognitive functioning in breast cancer survivors.65 They identified 4 cross-sectional studies that measured cognitive impairment in breast cancer survivors.66,67,68,69,70 All 4 studies found some degree of cognitive impairment.

Schagen and associates66demonstrated significantly more cognitive impairment in patients who received standard-dose chemotherapy than in control subjects (odds ratio [OR] 6.4, 95% CI 1.5 to 27.6; p = 0.013) at 2 years after therapy. In this study, there was no correlation between subjective reports of cognitive impairment and results of objective neuropsychological testing.

Van Dam and colleagues compared cognitive functioning in 34 patients who had received a high-dose chemotherapy regimen, 36 patients who had received a standard-dose regimen and 34 control patients who had received no chemotherapy; the average time since completion of chemotherapy was 2 years.67 Patients who received the high-dose chemotherapy had a risk of cognitive impairment 8.2 times higher (95% CI 1.8 to 37.7; p = 0.006) than that of the control subjects and 3.5 times higher (95% CI 1.0 to 12.8; p = 0.056) than that of patients who received the standard-dose regimen. These results were not related to anxiety, depression or fatigue. There was no correlation between subjective reports of cognitive functioning and results of objective neuropsychological testing. A follow-up report of this study at 4 years after therapy showed an improvement in cognitive functioning in both chemotherapy groups in terms of self-reported problems and neuropsychological test results.70

Brezden and colleagues68 found that 31 patients receiving chemotherapy at the time of the study had worse cognitive functioning than either control subjects or 40 patients who had completed chemotherapy 2 years previously. These differences, however, were not statistically significant.

Ahles and colleagues69 studied cognitive functioning in 35 patients 10 years after they completed standard-dose chemotherapy and found that it was significantly worse than that of breast cancer patients who had received local therapy only.

In a recent study by Tchen and colleagues, 110 women receiving adjuvant chemotherapy for breast cancer were matched with a disease-free control group not receiving chemotherapy.71 There was a higher incidence of moderate or severe cognitive impairment in the treatment group than in the control group (16% v. 4%; p = 0.008). In addition, chemotherapy patients experienced more fatigue, more menopausal symptoms and worse quality of life.

Although these studies point to an effect of chemotherapy on cognitive functioning, given the limited strength of the evidence, it is premature to recommend routine neuropsychological testing or interventions. All of the studies had methodological problems, such as lack of baseline data to assess cognitive functioning before treatment, small samples, and inability to control for hormonal factors and tamoxifen use. Furthermore, the evidence is conflicting as to whether the duration of the effect is short term or long term. As well, 2 of the studies found no correlation between subjective complaints and objective measures of cognitive functioning. Physicians should assess and treat patients with emotional distress, which may be the underlying cause of subjective complaints of impaired cognitive functioning. Prospective longitudinal controlled studies are needed in order to better understand the relation between chemotherapy and cognitive impairment.


Fatigue is experienced by most breast cancer patients during treatment.72,73 However, the prevalence of fatigue at 1 year after treatment has been estimated to be between 17%74 and 38%.72,75

The causes of fatigue after breast cancer treatment have not been determined. The potential relation between fatigue and initial treatment has been investigated. Three studies found fatigue to be unrelated to the type of treatment received, the use of tamoxifen or the time since treatment.72,75,76 In one case–control study involving 61 disease-free patients between 3 and 36 months after treatment, Broeckel and colleagues73 found that, compared with control subjects, breast cancer survivors had more severe fatigue (p < 0.01) and more current fatigue (p < 0.05). However, they included only patients who had received chemotherapy, which makes it impossible to determine whether it was the chemotherapy or other aspects of the cancer treatment and diagnosis that were the underlying factors. Bower and associates72 surveyed 1957 disease-free breast cancer survivors between 1 and 5 years after the initial breast cancer diagnosis. Women who received radiotherapy or chemotherapy or both reported higher levels of fatigue at 1 year after diagnosis than those who did not receive such therapy (p = 0.02); after 1 year the difference in fatigue scores associated with treatment was no longer statistically significant. Woo and colleagues77 found higher fatigue scores among women who received combination treatment (i.e., chemotherapy plus radiotherapy) than among those receiving other forms of treatment. However, the very poor response rate of 15% suggests that this was a biased sample. Furthermore, women were surveyed within only 18 months after treatment.

Multivariate analysis in the study by Bower and associates72 found that the most important predictors of fatigue were depression (OR 1.13; p = 0.0001) and pain (OR 0.97; p = 0.0001). The type of treatment received (radiation, OR 1.23, p = 0.19; chemotherapy, OR 1.29, p = 0.18; radiation plus chemotherapy, OR 1.23, p = 0.25) was not associated with fatigue in the multivariate analysis. Bower and associates also found that breast cancer survivors reported slightly higher levels of energy than age-matched women in the general population (p = 0.009). In another study, Okuyama and colleagues found that depression was an important predictor of fatigue.76

Fatigue is experienced by many breast cancer survivors. Based on current evidence, the mechanism of fatigue and the relation between fatigue and primary treatment modality remain unclear. Fatigue in breast cancer survivors should be approached by first investigating and ruling out known physiologic causes. In addition, physicians should assess and treat patients with depression or pain, which may be underlying causes of fatigue. Prospective longitudinal controlled studies are needed to better understand the prevalence and cause of fatigue in breast cancer survivors.

Weight management

Weight gain is a common problem for breast cancer survivors.78,79 It has been associated with receipt of adjuvant chemotherapy78,80 but not with tamoxifen therapy (level I evidence).37 Weight gain has a negative impact on HRQL81 and weight-related illnesses.78,82 There is a growing body of knowledge that shows an association between obesity at diagnosis or weight gain after diagnosis and breast cancer outcomes such as recurrence and survival.82

Chlebowski and colleagues82 conducted a systematic review of the relation between obesity at diagnosis and breast cancer outcomes. They identified observational studies only and did not perform a meta-analysis. Of 34 studies identified, 26 (involving a total of 29 460 patients) showed a statistically significant association between obesity (measured in various ways) and breast cancer recurrence or survival; 8 studies (involving a total of 3727 patients) found no such associations. In an earlier report of a meta-analysis, a hazard ratio for the effect of increased body weight on breast cancer recurrence at 5 years was 1.78 (95% CI 1.50 to 2.11), and the effect on death at 10 years was 1.36 (95% CI 1.19 to 1.55).83

The National Surgical Adjuvant Breast and Bowel Project (NSABP) recently examined the relation between obesity and outcomes in 3385 patients with node-negative breast cancer enrolled in the NSABP B-14 trial that compared tamoxifen therapy with placebo.84 Breast cancer recurrence among obese women was the same as that among underweight and normal-weight women (level I evidence). All-cause mortality was higher among obese women than among normal-weight women, but breast cancer mortality was not increased among obese women.

In a recent analysis involving 5204 women in the Nurses' Health Study, weight before diagnosis and weight gain after diagnosis were associated with increased breast cancer recurrence and breast cancer mortality among women who never smoked compared with past and current smokers.85,86

Clinical practice guidelines on weight management for the general population have been published.87 However, the direct application of these interventions to breast cancer survivors remains to be determined. Three randomized controlled trials are evaluating the impact of dietary interventions on weight control and breast cancer prognosis.88,89,90 In a recent survey 41% of patients reported making positive dietary changes in the 12 months after diagnosis, which suggests that breast cancer survivors are receptive to initiating dietary change.81

Research suggests that weight gain is more likely among patients who have received adjuvant chemotherapy than among patients who did not receive chemotherapy.78 The weight gain appears to be due to a decrease in physical activity rather than an increase in energy intake, and it is associated with a change in body composition involving an increase in body fat relative to lean body mass.78 Although these changes are consistent with the onset of menopause, in a prospective cohort study involving 535 patients followed for 1 year, Goodwin and associates found that chemotherapy and menopause were independent predictors of weight gain (all p ≤ 0.05).79 They also found that tamoxifen therapy did not predict weight gain among patients followed for 1 year after diagnosis.79 Similarly, in a prospective cohort study involving 200 breast cancer patients who did not receive chemotherapy, there was no difference in weight gain up to 5 years after diagnosis between those who received tamoxifen and those who did not (mean gain 1.2 kg; 95% CI for the difference –1.8 to 1.2; p = 0.66).91 In a randomized controlled trial involving women at high risk of breast cancer, tamoxifen therapy was not associated with weight gain compared with placebo (level I evidence).37 Although this is strong evidence against the impact of tamoxifen on weight gain, it should be noted that the study involved women at high risk of breast cancer rather than breast cancer survivors.

There is an increasing body of evidence showing a positive association between obesity at diagnosis or weight gain after diagnosis and breast cancer outcomes, although at this time there is no definitive evidence that losing weight after diagnosis influences breast cancer outcomes. However, given the positive effect of weight management on other important comorbid conditions that can affect breast cancer survivors,87 a discussion with patients about weight management and effective weight-management measures is recommended.


Women with a history of breast cancer may be at increased risk of osteoporosis owing to premature ovarian failure resulting from chemotherapy.92,93,94,95 In addition, preliminary results of trials of aromatase inhibitors as adjuvant treatment for breast cancer in postmenopausal women suggest increased rates of fractures and osteoporosis with the use of these agents.96,97,98,99,100

Current Canadian guidelines from the Osteoporosis Society of Canada recommend that healthy postmenopausal women with no risk factors for osteoporosis other than age undergo a screening bone mineral density test with dual-energy x-ray absorbtiometry after age 65.101 Women with risk factors for osteoporosis may be screened at an earlier age.101 Aromatase inhibitor therapy and premature ovarian failure are considered major risk factors for osteoporosis.102 Hence, these guidelines can be extrapolated to women with a history of breast cancer. Women given aromatase inhibitors should have a baseline bone mineral density test and be monitored closely for the development of osteoporosis. There is no clear evidence regarding the frequency of bone mineral density monitoring in these patients. In such situations, clinicians should refer to published guidelines for the treatment and monitoring of osteoporosis in women with other high-risk factors.

The American Society of Clinical Oncology guideline on bisphosphonates commented on bone health in women with a history of breast cancer.102 The guideline recommends that women with breast cancer at high risk of osteoporosis (e.g., age > 65 years, family history of osteoporosis or premature menopause because of treatment) should undergo a screening bone mineral density test and, depending on the results, be given bisphosphonate treatment. As is done for healthy women, follow-up surveillance for women with breast cancer should include timely bone mineral density tests and bisphosphonate treatment if the density is falling.92,101

A number of randomized controlled trials involving healthy women have demonstrated the efficacy of bisphosphonates in the treatment of osteoporosis.103,104,105,106 Canadian osteoporosis guidelines recommend bisphosphonates as first-line agents for the treatment of osteoporosis.101 For women with breast cancer, bisphosphonates such as clodronate and risedronate have been investigated for the prevention of skeletal metastases.92,107,108 Bone mineral density was a secondary outcome in these studies. There was significantly less decrease in bone mineral density associated with the bisphosphonate therapy than with placebo among women with early breast cancer.92,107,108 Similarly, studies support bisphosphonate therapy for the treatment or prevention of aromatase-inhibitor–induced bone loss.109,110 Women should also be counselled regarding the importance of bone health and adequate intake of calcium and vitamin D through diet or supplementation and exercise.101 A number of recent studies have evaluated the effectiveness of bisphosphonates for the prevention of skeletal metastases, and the results are conflicting.111,112,113,114,115,116 Hence, it is premature to make recommendations regarding the use of bisphosphonates for such prevention.

Intranasal calcitonin therapy has been approved for use in the general population for the treatment of osteoporosis and has been shown to reduce pain associated with acute vertebral fractures (level I evidence).101 However, no studies of calcitonin specifically involving women with breast cancer have been reported.

Tamoxifen, by virtue of its proestrogenic effects, preserves bone mineral density in postmenopausal women. However, its use has been associated with loss of bone mineral density in premenopausal women.117 Raloxifene, like tamoxifen, is a selective estrogen-receptor modulator with proestrogenic effects on bone metabolism. Although raloxifene and bisphosphonates are considered first-line therapies in the prevention and treatment of postmenopausal osteoporosis101 (level I evidence), there are few data on the safety of raloxifene in women with a history of breast cancer.118 Therefore, raloxifene is not recommended for use in women with a history of breast cancer. This recommendation is based on the fact that the drug is similar to tamoxifen, and 10 years of tamoxifen use has been associated with increased breast cancer recurrence compared with 5 years of tamoxifen use.119,120 Also, laboratory studies show that raloxifene may stimulate tamoxifen-dependent cells.121

Although estrogen replacement therapy reduces the loss of bone mineral density associated with menopause, its use is contraindicated in women with a history of breast cancer because of concerns of precipitating breast cancer recurrence.122 Recently, a clinical trial that randomly allocated women with a history of breast cancer to receive either hormone replacement therapy or none was stopped because of an increased risk of a new breast cancer.123

Sexual functioning

Decreased sexual desire, decreased frequency of intercourse, dyspareunia and difficulties with orgasm have been commonly reported in women with breast cancer.124,1254,126 However, in most studies, sexual functioning of breast cancer survivors appears to be similar to that of healthy, age-matched women.124,127,128 The highest incidence of sexual dysfunction among women treated for breast cancer has been reported among those who received chemotherapy.125,126 Except for giving rise to more vasomotor symptoms, treatment with tamoxifen, compared with no systemic treatment, has no effect on sexual functioning. 129 Ganz and colleagues investigated predictors for sexual interest, dysfunction and satisfaction using a multivariate regression analysis in a cohort of breast cancer survivors.130 Significant predictors of sexual interest included having a new partner since the diagnosis of breast cancer (more sexual interest; p ≤ 0.05), having a better mental health score (more sexual interest; p ≤  0.01) and having a poorer body image score (less sexual interest; p ≤ 0.001). Predictors of sexual dysfunction were vaginal dryness (more sexual dysfunction; p ≤ 0.001), past chemotherapy use (more sexual dysfunction; p ≤ 0.05) and having a new partner since diagnosis (less sexual dysfunction; p ≤ 0 .05). Quality of the partnered relationship (better relationship score associated with greater sexual satisfaction; p ≤ 0.001) and sexual problems in the partner (less sexual satisfaction; p ≤ 0.001) were significant predictors of sexual satisfaction.

A number of studies have shown that, although the type of surgery may have an impact on body image, sexual functioning is not adversely affected.131,132,133 A meta-analysis of studies of psychosocial consequences of surgery for breast cancer showed modest effects for the impact of the type of surgery on sexual functioning.134

Ganz and colleagues tested the efficacy of an intervention program consisting of a comprehensive menopausal assessment that was offered to 76 perimenopausal or postmenopausal women with a history of breast cancer.135 The intervention was delivered by a trained nurse-practitioner and focused on symptom assessment, education, counselling and specific pharmacologic and behavioural interventions as appropriate. Sexual functioning was significantly improved in the group receiving the intervention compared with the usual-care group (p = 0.04; level I evidence).

Many of the studies investigating sexual functioning of breast cancer survivors were retrospective or used qualitative methodology. There is a need for prospective collection of data, particularly from randomized trials involving women receiving chemotherapy with long-term follow-up.

Sexual functioning should be discussed with women in follow-up visits. Interventions to decrease menopausal symptoms (especially vaginal dryness) should be discussed and may aid in improving sexual functioning.136 Recommendations for the treatment of menopausal symptoms have been made in an evidence-based guideline published previously (see guideline 14).


Because many women of child-bearing age are diagnosed with breast cancer, issues of subsequent pregnancy become important. The high levels of estrogen associated with pregnancy have raised concerns about stimulating dormant micrometastases in breast cancer survivors. A number of case series and case–control studies evaluating survival following pregnancy after breast cancer diagnosis have been published.137,138,139,140,141,142,143,144,145,146,147,148,149,150,151 Most studies have shown that subsequent pregnancy in breast cancer survivors does not adversely affect survival.137,138,140,143,144,149–151 However, these studies involved small numbers of patients and were retrospective in nature, which makes them susceptible to significant biases. Also, most of the studies lacked an appropriately matched control group or involved highly selected patients. No prospective studies have been reported, and a randomized controlled trial is clearly not feasible.

Decisions about pregnancy should be discussed between the patient and her physician. The decision should balance the unknown effect of pregnancy on breast cancer outcomes against the concern of declining fertility with increasing age. In addition, pregnancy within 5 years after the diagnosis of breast cancer will probably necessitate the early discontinuation of adjuvant endocrine therapy, which would result in a decreased benefit. There does not appear to be an increase in congenital defects in infants of women who have been treated with chemotherapy before pregnancy. 152

This article has been peer reviewed.

Acknowledgements: We thank the following for their valuable advice: Dr. Patricia Ganz, Jonsson Comprehensive Cancer Center, Los Angeles, Calif.; Dr. Pamela Goodwin, Mount Sinai Hospital, Toronto, Ont.; and Dr. Eric Winer, Dana-Farber Cancer Institute, Boston, Mass.

The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer: Chair: Dr. Mark Levine (Cancer Care Ontario), Juravinski Regional Cancer Centre and McMaster University, Hamilton, Ont. Members: Dr. Penny Barnes, Queen Elizabeth II Health Sciences Centre, Halifax, NS; Dr. Judy Caines (Federal/Provincial/Territorial Advisory Committee on Health Services), Nova Scotia Cancer Centre, Halifax, NS; Dr. Beverley Carter (Health Care Corporation of St. John's), St. Clare's Mercy Hospital, St. John's, Nfld.; Dr. Eva Grunfeld (College of Family Physicians of Canada), Cancer Care Nova Scotia, Halifax, NS; Dr. Ivo Olivotto (BC Cancer Agency), Vancouver Island Cancer Centre and University of British Columbia, Victoria, BC; Dr. Carol Sawka, Cancer Care Ontario, Toronto, Ont.; Dr. Hugh Scarth (Atlantic Health Sciences Corporation), Saint John Regional Hospital, Saint John, NB; and Dr. Timothy Whelan (Cancer Care Ontario), Juravinski Regional Cancer Centre and McMaster University, Hamilton, Ont.

Correspondence to: Dr. Mark Levine, Rm. 104, Henderson Research Centre, Henderson Hospital, 711 Concession St., Hamilton ON L8V 1C3; fax 905 389-9288


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