Approach to the patient following treatment for breast cancer

INTRODUCTION — According to statistics from the International Agency for Research on Cancer (IARC), there are approximately 44 million people living with cancer worldwide [1]. In the United States, the five-year survival rate for female breast cancer is approximately 90 percent [2]. Additionally, although the vast majority of breast cancer survivors are women, approximately 2500 men are diagnosed with breast cancer annually in the United States alone, and most will achieve long-term disease-free survival [3]. (See "Breast cancer in men".)

Patients who are living for decades beyond cancer experience the normal issues of aging, which are often compounded by the long-term effects of having had cancer and cancer therapy. These patients are at risk for a breast cancer recurrence (which is most common in the first five years but may occur even decades following treatment), a new primary breast cancer, other cancers, and short-term and long-term adverse effects of treatment. Additional issues for cancer survivors relate to psychologic, genetic, reproductive, social, and employment concerns.

Unfortunately, there is a lack of clear evidence surrounding many issues for what constitutes best practices in caring for patients with a history of cancer, and this contributes to wide variation in care [4]. Recommendations for post-treatment surveillance after primary therapy of breast cancer will be reviewed here. Detailed discussions of prognosis, the patterns of relapse (ie, locoregional recurrence, second primary breast tumor, metastatic disease), and long-term complications of breast cancer therapy are presented separately. (See "Overview of the treatment of newly diagnosed, invasive, non-metastatic breast cancer", section on 'Prognosis' and "Prognostic and predictive factors in early, non-metastatic breast cancer" and "Overview of long-term complications of therapy in breast cancer survivors and patterns of relapse".)

A general overview of cancer survivorship is covered separately. (See "Overview of cancer survivorship care for primary care and oncology providers".)

DEFINING A CANCER SURVIVOR — There are many definitions and phases of cancer survivorship. We define a cancer survivor as any person with cancer, starting from the moment of diagnosis. This is consistent with definitions from the National Coalition for Cancer Survivorship [5] and the National Cancer Institute [6]. By this definition, there are more than four million breast cancer survivors in the United States, including over 150,000 living with overt metastatic disease [7].

This overview addresses breast cancer survivors who have completed initial treatment for breast cancer (ie, surgery, chemotherapy, and/or radiation therapy) and who are without evidence of disease.

GUIDELINES FOR POST-TREATMENT FOLLOW-UP — Guidelines from the American Society of Clinical Oncology (ASCO) suggest that patients with early-stage breast cancer (tumor <5 cm and fewer than four positive nodes) may follow up exclusively with a primary care provider (PCP); for patients and clinicians who agree with this plan, care may be transferred approximately one year after diagnosis [8]. In such cases, both the patient and the PCP should be advised of the appropriate follow-up and management strategy.

Additional guidelines for post-treatment follow-up were made by the Institute of Medicine; these are discussed separately. (See "Overview of cancer survivorship care for primary care and oncology providers", section on 'Components of posttreatment follow-up'.)

Prognosis of nonmetastatic breast cancer is discussed elsewhere. (See "Overview of the treatment of newly diagnosed, invasive, non-metastatic breast cancer", section on 'Prognosis' and "Prognostic and predictive factors in early, non-metastatic breast cancer".)

Data are sparse to inform optimal follow-up of male breast cancer survivors; recommendations for women are usually applied to men, with modification as appropriate.

For patients receiving adjuvant hormonal therapy, informed decisions regarding long-term options may necessitate periodic referral for oncology assessment since treatment strategies are evolving over time. Furthermore, input from an oncology specialist is warranted if there is suspicion or evidence of disease recurrence, or if questions arise regarding the safety of certain interventions (eg, vaginal estrogen in a patient who has atrophic vaginitis).

Breast cancer survivors should receive ongoing age-appropriate screening studies and preventive care, consistent with recommendations for the general population, for conditions other than those related to breast cancer and its treatment. (See "Overview of preventive care in adults".)

COMPONENTS OF FOLLOW-UP — Components of follow-up are discussed below and in the algorithm (algorithm 1).

History and physical examination — History and physical examination have been the principal means of detecting a breast cancer recurrence [9-11]. We suggest that patients be seen every three to six months during the first three years after primary therapy, every 6 to 12 months for the next two years, and then annually (table 1), consistent with the American Society of Clinical Oncology (ASCO) 2015 guidelines [12]. However, this schedule is arbitrary; no studies have evaluated the benefit of less frequent clinical visits in patients with low-risk disease or more frequent visits in those with higher-risk disease [13].

History — In addition to the general components of a medical history, the breast cancer survivor should be screened for symptoms of local recurrence as well as metastatic disease. Patients should also be asked about their adherence to any adjuvant treatments that have been recommended. Any changes in the family history should be obtained, which may be important to discussions regarding genetic counseling. (See 'Genetic counseling' below.)

The history should include any interval changes in the patient's social environment (including partner status, life events, living arrangements, and occupational issues) that may have arisen since the end of treatment.

A review of systems should not only screen for metastatic disease but also may identify issues related to prior treatment. We suggest that the review of systems include the following [14,15]:

●Constitutional symptoms – Anorexia, weight loss, malaise, fatigue, insomnia.

●Bone health – Presence of pain and its characteristics (ie, location, character of pain [dull or aching], chronic or intermittent, associated symptoms, exacerbating factors, and what provides relief).

●Pulmonary symptoms – Persistent cough or dyspnea (at rest or with exertion).

●Neurologic symptoms – Headache, nausea, vomiting, confusion, weakness, numbness, or tingling.

●Gastrointestinal symptoms – Right upper-quadrant pain, change in bowel habits, presence of bloody or tarry stools.

●Genitourinary symptoms – Vaginal bleeding, pelvic pain, difficulty urinating.

●Psychological symptoms – Depression, anxiety.

●Reproductive/endocrine symptoms – Hot flashes, dyspareunia, vaginal dryness, sexual dysfunction, fertility concerns (in women with intact ovarian function).

Physical examination — We suggest that a complete physical examination be performed at each visit, which is consistent with ASCO guidelines [12]. At a minimum, the examination should include [14,15]:

●Examination of the breast, chest wall, and axilla – Thorough examination should be performed of the affected breast (if preserved) or the chest wall, the contralateral side, the bilateral axillary regions, and the supraclavicular fossas. For those patients who underwent breast-conserving treatment, providers should be comfortable examining the previously irradiated breast.

The breast examination in patients who underwent adjuvant radiation therapy may not be helpful. In a review summarizing the results of seven randomized clinical trials, the sensitivity and specificity of physical examination ranged from 29 to 74 percent and from 17 to 30 percent, respectively [16]. (See "Overview of long-term complications of therapy in breast cancer survivors and patterns of relapse".)

Diagrams of the affected breast, including postoperative and postradiotherapy changes, can be helpful in documenting and following the examination over time.

Evidence of local recurrence includes newly discovered lumps (on the skin, within the breast, or the nodal regions). Other worrisome findings may include skin changes in the breast (table 2). For women who have undergone mastectomy with or without breast reconstruction, the incision site and the surrounding skin of the chest wall should be examined visually and palpated for abnormalities.

●Musculoskeletal examination – If lymphedema is suspected, examination of the arms should include circumferential measurement of the upper extremities bilaterally. (See "Clinical features and diagnosis of peripheral lymphedema".)

In addition, palpation of the spine, sternum, ribs, and pelvis for bone tenderness should be routinely performed.

●Lung examination – Evaluation for breath sounds and percussion changes.

●Abdominal examination – Evaluation for right upper quadrant tenderness and/or organomegaly.

●Cardiac examination – Evaluation for heart failure. (See "Determining the etiology and severity of heart failure or cardiomyopathy", section on 'Physical examination'.)

●Neurologic examination – Evaluation of balance, gait, and sensory and motor function. (See "The detailed neurologic examination in adults".)

●Gynecologic examination – Regular gynecologic follow-up should be performed for women who have not undergone total hysterectomy (table 1) [12]. This is particularly important in women who are receiving tamoxifen because of the increased risk for endometrial tumors. (See "Managing the side effects of tamoxifen and aromatase inhibitors".)

Breast imaging

Mammography — The purpose of post-treatment mammographic surveillance is to detect ipsilateral local recurrences after breast-conserving therapy (BCT), which develops in up to 4 percent of women treated for early breast cancer [17]. In addition, mammography is performed as surveillance for a contralateral breast cancer. There is a lack of high-quality evidence to inform the optimal timing, methodology, and survival benefit of mammographic surveillance for detecting ipsilateral recurrence or a contralateral breast cancer [18,19]. For women in long-term follow-up, mammographic surveillance should be obtained annually.

We typically obtain a diagnostic mammogram annually for the first three to five years after diagnosis [20], and then switch to screening mammograms afterwards, although practice is variable across institutions. The rationale for diagnostic mammography during the first few years after diagnosis is that it detects recurrences and residual disease in a small percentage of cases and establishes a new baseline, as postsurgical and postradiation changes typically stabilize at three years. The views obtained in a diagnostic mammogram are tailored to evaluate a specific area, unlike in a screening mammogram. The difference between screening versus diagnostic mammography is discussed in more detail elsewhere. (See "Breast imaging for cancer screening: Mammography and ultrasonography", section on 'Screening versus diagnostic mammography'.)

Although the evidence is limited, surveillance mammography of residual breast tissue after BCT or unilateral mastectomy appears to be associated with a reduction in mortality among women of all ages [19,21,22]. This was illustrated best in a 2008 case-control study that compared mammographic utilization in women over 65 years who died or did not die of breast cancer and who lived at least 30 months following breast cancer diagnosis [21]. Women who had undergone a surveillance mammogram within one year were less likely to die of breast cancer (odds ratio [OR] 0.83, 95% CI 0.72-0.95).

Local recurrence — There are no prospective trials that address the utility of mammography in the detection of local recurrence. Data from retrospective series suggest that mammography detects earlier lesions with a more favorable prognosis and that survival is improved in women whose lesions are detected mammographically as compared with those detected by other means [23-25]. However, other data suggest that mammographic screening in women with a personal history of breast cancer performs less well (lower sensitivity and slightly lower specificity) than in women without such a history [26]. In one study, women with a personal history of breast cancer had a higher rate of interval cancers compared with women without a history of breast cancer [26]. Fortunately, the majority of both screen-detected and interval cancers were early stage. (See "Clinical manifestations and evaluation of locoregional recurrences of breast cancer".)

Contralateral breast cancer — There are no randomized trials that address the role of mammography or its impact on survival in detecting contralateral breast cancers. However, recommendations for mammographic surveillance are based upon the benefits seen in the general population without a history of breast cancer. In general, breast cancer survivors are higher-risk women than the general population, and it would seem reasonable to infer that they derive as much or even more benefit from mammography of the contralateral breast. (See "Screening for breast cancer: Strategies and recommendations".)

There is indirect evidence from retrospective series that supports a beneficial impact for mammography of the contralateral breast [27-29]. One study compared outcomes among a cohort of breast cancer survivors in which both physical examination and mammography were performed for post-treatment follow-up versus a separate cohort of women who were followed only by physical examination [27]. Although the frequency of contralateral breast cancer was similar in both groups, more recurrences were node-negative in the women with utilization of routine mammography (75 versus 57 percent, respectively). Furthermore, the contralateral tumors were more often smaller than 10 mm or in situ (noninvasive) (35 versus 7 percent, respectively) in women undergoing routine mammography.

Breast MRI — Breast magnetic resonance imaging (MRI) is not routinely recommended for breast cancer survivors because of a lack of demonstrated benefit in this population. However, we obtain breast MRI for breast cancer survivors in the following circumstances:

●For women who have undergone breast conserving therapy who are at high risk for a second primary (>20 percent lifetime risk), for example, based on a known breast cancer-associated gene mutation [12,30-32] (see "Overview of hereditary breast and ovarian cancer syndromes"). This practice is extrapolated from the indications for breast MRI as a screening tool in high-risk women. (See "MRI of the breast and emerging technologies", section on 'Screening high-risk women'.)

●For patients suspected of a breast cancer recurrence (eg, on the basis of physical exam),

•After breast conserving therapy when mammography, with or without breast ultrasound, is inconclusive [33].

•After mastectomy, if ultrasound has been inconclusive.

Multiple studies have suggested no benefit for routine screening MRI in breast cancer survivors. In a 2012 systematic review that included 10 case series and 494 breast cancer survivors, the sensitivity and specificity of MRI to detect recurrent breast cancer was no better than mammography, historically [34]. In a meta-analysis of 16 studies in patients with prior breast cancer who underwent mastectomy (with or without reconstruction), MRI screening was associated with a cancer detection rate of 5.2 per 1000 screening exams (0.5 percent); however, the majority of detected cancers were palpable, arguing against routine MRI screening in the absence of physical exam findings [35].

Ultrasound — Routine use of breast ultrasound (US) as part of surveillance is not recommended.

The addition of breast US to screening mammography was evaluated in a trial in which 2809 women with an elevated risk for breast cancer who were undergoing routine screening mammography were randomly assigned to mammography alone or with breast US [36]. Compared with mammography alone, ultrasound plus mammography increased the diagnostic yield (from 8 to 12 per 1000 women, 95% CI 1.1-7.2) but also increased the rate of false-positive results (4.4 versus 10.4 percent) and therefore lowered the positive predictive value.

In a meta-analysis among women with breast cancer who underwent mastectomy (with or without reconstruction), the cancer detection rate with routine ultrasonographic screening was just 2.7 per 1000 exams (0.3 percent), but the majority of detected cancers were palpable, arguing against ultrasound screening in patients lacking physical exam findings [35].

Surveillance of reconstructed breasts — For women who have undergone mastectomy, surveillance is usually performed by physical examination. Routine mammographic imaging is technically limited in patients who have prosthetic implants and is generally not advocated. However, mammography is technically feasible following autogenous myocutaneous flap reconstruction, particularly following transverse rectus abdominis musculocutaneous (TRAM) or perforator flap reconstruction because abdominal adipose tissue forms the bulk of the reconstructed breast [37]. Although the available data are sparse, and there is no consensus on this issue, some institutions image TRAM-reconstructed breasts using mammography since even after mastectomy, some normal tissue may be left on the chest wall from which a new breast cancer may on occasion arise, although the value of this is unclear and likely limited. (See "Overview of breast reconstruction".)

The only place where cancer can occur is either right below the skin in the subcutaneous tissue or just over the pectoralis muscle. Physical examination remains the cornerstone of detection of recurrent breast cancer after reconstruction, and other modalities such as MRI should be used only as adjuncts to clarify any physical findings. In a meta-analysis including women who underwent mastectomy and reconstruction for breast cancer, MRI surveillance resulted in a cancer detection rate of 4.7 per 1000 screening exams, but only 1.1 per 1000 were clinically occult (nonpalpable) [35].

Although the FDA recommends MRI or ultrasound screening of silicone implant reconstructed breasts after five to six years and every two to three years thereafter for possible rupture, it is not clear how this impacts outcomes and recent data suggest that this is not routine practice [38]. MRI screening for rupture of implants is typically done without gadolinium, and would not detect most recurrences. (See "Overview of breast reconstruction", section on 'Surveillance of the reconstructed breast'.)

Discontinuing breast imaging — Continued screening mammography is warranted for older survivors with reasonable functional status and life expectancy [39]. The available data suggest that surveillance mammography reduces the risk of death from breast cancer, even among older women [19,21]. We adopt the following approach: imaging 6 to 12 months after completion of local therapy followed by mammography annually for healthy women versus cessation of screening mammography in patients whose life expectancy is less than 5 to 10 years [40].

One prospective study evaluated over 1800 women 65 years and older with stage I and II breast cancer and reported that each additional mammogram was associated with a significant reduction in the risk of dying from breast cancer (OR 0.69, 95% CI 0.52-0.92) [19]. A similar conclusion was reached in a study from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database [21].

Evaluation of bone density — Women with a history of breast cancer may be at increased risk of osteoporosis as a result of prior cancer treatment. Therefore, ASCO guidelines include performing a baseline screening evaluation (typically with dual energy X-ray absorptiometry) in the following patients [41]:

●Women over age 65.

●Women ages 60 to 64 in the presence of any of the following: a family history of osteoporosis, body weight <70 kg, a history of a nontraumatic fracture, or other risk factors for osteoporosis (eg, smoking, a sedentary lifestyle, alcohol use).

●Postmenopausal women taking an aromatase inhibitor (AI), including those in whom an AI has been recommended but not yet initiated.

●Premenopausal women who develop treatment-related premature menopause.

However, it is not clear that bone density assessments are valuable at baseline if the patient already plans to initiate bisphosphonate or receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor therapy, regardless of the results. In that case, a bone density assessment at the completion of the bisphosphonate or RANKL inhibitor treatment may be of greater value, and this is our approach. Also, it is not clear what role vitamin D supplementation should play in women treated for breast cancer, nor whether levels should be checked routinely. In the absence of prospective data to inform the benefits specifically in these patients, the assessment of vitamin D levels and the role of vitamin D supplementation for women with low vitamin D levels should follow similar guidance as for women without a prior history of breast cancer. (See "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment" and "Calcium and vitamin D supplementation in osteoporosis".)

Further discussion related to bone health, including the screening, treatment, and surveillance of osteoporosis, for women treated for breast cancer is discussed separately. (See "Screening for osteoporosis in postmenopausal women and men" and "Use of osteoclast inhibitors in early breast cancer" and "Evaluation and management of aromatase inhibitor-induced bone loss".)

Genetic counseling — Breast cancer survivors who have not already pursued genetic testing may be appropriate candidates for testing. BRCA testing is an especially important consideration for men, and for women diagnosed at or under the age of 50, or with Ashkenazi heritage, and/or a strong family history of breast or ovarian cancer [39]. If the breast cancer was triple negative (not expressing estrogen receptor [ER], progesterone receptor [PR], or overexpressing human epidermal growth factor receptor 2 [HER2]), testing should be considered if a woman was diagnosed up to age 60. Prior to testing, it is important that patients be counseled about the potential ramifications of test results for themselves and their caregivers, both medically and psychosocially. (See "Genetic testing and management of individuals at risk of hereditary breast and ovarian cancer syndromes" and "Breast cancer in men".)

Other rarer genetic syndromes that predispose to breast cancer and for which testing can be performed, depending on family and personal history of a variety of cancers, include Li-Fraumeni and Cowden syndromes. A genetic counselor can help to discern whether such testing might be in order. (See "Li-Fraumeni syndrome" and "PTEN hamartoma tumor syndromes, including Cowden syndrome".)

Genetic testing of the breast cancer survivor is important, particularly to facilitate testing in other family members. Once a particular mutation has been identified, testing other family members is technically straightforward. While it is possible to begin the genetic testing process in an unaffected individual, there is a greater chance that these results will be inconclusive. Therefore, the breast cancer survivor should be tested, particularly if her own children and first-degree relatives are also interested in their personal genetic susceptibility. (See "Genetic testing", section on 'Practical issues'.)

Role of laboratory evaluation and other imaging — Intensive laboratory and/or radiologic surveillance is not indicated for asymptomatic breast cancer survivors. This was demonstrated in a 2005 meta-analysis of two randomized trials that compared routine follow-up (regular physical examination and mammography) with intensive surveillance (including radiologic and laboratory testing) [42]. There was no difference between groups in overall survival (hazard ratio [HR] 0.96, 95% CI 0.80-1.15) or disease-free survival (HR 0.84, 95% CI 0.71-1.00).

Early diagnosis of metastatic disease, based on imaging alone and prior to onset of clinical signs or symptoms, may result in earlier intervention, with associated toxicities, but does not improve survival. Although a small percentage of patients with limited metastatic disease (eg, isolated pulmonary or liver metastases) may be treated with a multimodality approach, whether such patients are best identified by intensive post-treatment surveillance is unknown. Furthermore, laboratory and imaging tests used for surveillance have significant false-positive and false-negative rates and increased costs [43]. The unnecessary additional testing generated by a false-positive result and the misleading reassurance generated by a false-negative test can adversely affect the breast cancer survivor.

Therefore, we recommend against performing the following tests in asymptomatic women (table 1) [12]:

●Liver function tests – Routine liver function tests are falsely elevated in up to 80 percent of women without liver metastases [44-46].

●Serum tumor markers – A number of serum markers are available that can detect early breast cancer recurrence, including CA 15-3, carcinoembryonic antigen (CEA), and CA 27.29 [47-50]. These biochemical markers of breast cancer increase in conjunction with advancing primary disease stage and reflect the total body burden of disease (table 3) [51-54]. However, they are neither sensitive nor specific for breast cancer relapse [50,51]. Therefore, measurement of serum tumor markers should only be used to monitor treatment response of patients with metastatic breast cancer in the absence of readily measurable advanced disease [55].

●Chest imaging – Neither chest radiograph nor computed tomography (CT) is recommended to screen for lung metastases in the asymptomatic patient [56-58]. In one series of 416 patients who were undergoing surveillance with routine chest imaging after completing primary treatment for breast cancer, only nine patients had isolated pulmonary metastases. [59].

●Bone scan and serum alkaline phosphatase – There is no evidence that early detection of bone metastases changes the clinical course of the disease. Metastases to bone are almost always diagnosed by symptoms, even when patients undergo routine surveillance with bone scans [60-63]. Bone scans have an estimated sensitivity and specificity for detecting bone metastases of approximately 86 and 81 percent, respectively [64].

Alkaline phosphatase is neither sensitive nor specific for bone metastases. In a series of 1601 patients with node-positive breast cancer, alkaline phosphatase was only elevated in one-half of those patients who had known skeletal metastases, while the test was abnormal in 28 percent of those without bone metastases [63].

●Abdominopelvic imaging – Neither liver ultrasound nor abdominopelvic CT scans is recommended as a routine component of post-treatment surveillance [65-67]. In one large series of over 2400 patients that included 6628 pelvic CT scans performed over a nine-year period, pelvic metastases were the only site of metastatic disease in 13 (0.5 percent) [66]. However, the findings led to over 200 additional radiographic and 50 surgical procedures, of which 84 percent yielded benign or negative results.

●PET scanning – There is no role for positron emission tomography (PET) scan in post-treatment follow-up. In retrospective cohort studies and a meta-analysis of 16 studies, PET scanning has been consistently more sensitive than conventional imaging and serum tumor markers for early diagnosis of recurrent disease [68-70]. However, the impact on survival and quality of life has not been addressed, and it seems unlikely that this approach would provide a survival or quality-of-life benefit.

●Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) – Available evidence does not support the use of tumor markers, CTCs, or, more recently available, ctDNA to evaluate for recurrence after treatment for primary breast cancer [55]. Although the presence of CTCs has been associated with worsened prognosis for those with early breast cancer, data are limited and do not support their use for routine clinical decision-making regarding adjuvant treatments or evaluation for recurrence. The presence of ctDNA has also been associated with recurrence in early and later follow-up after treatment for early breast cancer; however, the limited available data do not support routine use for decision-making in follow-up [71-73]. (See "Prognostic and predictive factors in early, non-metastatic breast cancer", section on 'Disseminated and circulating tumor cells'.)

PROMOTING A HEALTHY LIFESTYLE — Patients often ask what they can do to improve their overall outcome from breast cancer. Lifestyle modification can be an empowering and effective way to boost physical and mental health in breast cancer survivors and possibly to improve disease and overall mortality outcomes. Observational data suggest that exercise, avoidance of obesity, and minimization of alcohol intake are associated with a decreased risk of breast cancer recurrence and death in survivors [74-77].

Physical activity, diet, and body weight — Diet, physical activity, and weight are collectively considered energy balance factors because they describe the relationship between energy consumed (diet), energy expended (physical activity), and energy stored (adiposity). They have each been linked to cancer outcomes, particularly in survivors of breast cancer. (See "The roles of diet, physical activity, and body weight in cancer survivors".)

One nutritional issue of interest to breast cancer survivors is the impact of soy products (which contain phytoestrogens) on breast cancer recurrence rates. Although there is no convincing evidence that soy affects the risk of recurrence, the theoretical risk that phytoestrogens could stimulate the growth of hormonally sensitive cancers raises the concern that high soy intake could be dangerous. Thus, moderation of soy intake is generally suggested. (See "Factors that modify breast cancer risk in women".)

The safety and efficacy of many other nutritional complementary therapies including mistletoe, high doses of vitamins, and trace elements like selenium, zinc, and copper remains uncertain [78] (see "Overview of complementary, alternative, and integrative medicine practices in oncology care, and potential risks and harm"). Higher vitamin D levels at the time of diagnosis have been associated with better prognosis, especially in premenopausal women [79], but there are no randomized controlled trial data available to inform the potential impact of vitamin D supplementation on risk of recurrence.

Complementary therapies — Complementary therapies, including acupressure and mindfulness, music therapy, and yoga have been explored as treatments in cancer survivors. While there is no evidence that these interventions decrease recurrences, they may improve quality of life and mood [80].

In one trial of 424 survivors of nonmetastatic breast cancer randomly assigned to self-administered relaxing acupressure, stimulating acupressure, or usual care, both acupressure arms reduced persistent fatigue, and relaxing acupressure also improved sleep quality and quality of life [81]. Randomized trial data suggest some improvement of joint pain with true versus sham acupuncture among women on aromatase inhibitors [82]. (See "Adjuvant endocrine and targeted therapy for postmenopausal women with hormone receptor-positive breast cancer", section on 'Side effects'.)

Although breast cancer survivors may experience psychologic and physical side effects from their cancer diagnosis and treatment, some evidence suggests improvement in these symptoms with the practice of mindfulness [83-87]. Mindfulness involves being aware and accepting of one's present experiences, including thoughts, feelings, and physical sensations [84]. In one study of 322 breast cancer survivors randomly assigned to a six-week mindfulness-based stress reduction program or usual care, patients in the study group experienced improvement in a broad range of symptoms, including fear of recurrence, anxiety, and fatigue [83]. In another trial of 71 patients, mindfulness practices over six weeks led to reductions in stress and markers of inflammation. Improvements in fatigue, sleep, vasomotor symptoms, and affect were also observed [84]. However, at three-month follow-up, many of these benefits were not maintained, suggesting that ongoing practice of these techniques rather than one-time participation in a training program may be key to promoting lasting benefits. Long-term data on mindfulness practices as well as their applicability to a broader population of breast cancer survivors are pending.

Alcohol intake — The evidence that alcohol is associated with an increase in the risk of recurrence is limited [77,88-90]. In the largest study, 1897 female breast cancer survivors (on average two years postdiagnosis) participated in the Life After Cancer Epidemiology (LACE) study [77]. Those who drank ≥6 g of alcohol daily (equivalent to at least three to four alcoholic drinks per week) had significantly higher rates of recurrence (hazard ratio [HR] 1.35, 95% CI 1.0-1.83) and death due to breast cancer (HR 1.51, 95% CI 1.0-2.29) than those who drank <0.5 g daily. Overweight and postmenopausal women seemed to experience the greatest harm from alcohol intake as measured by breast cancer recurrence risk. (See "Overview of the risks and benefits of alcohol consumption", section on 'Breast cancer'.)

REPRODUCTIVE ISSUES

Fertility and pregnancy after breast cancer — Young breast cancer survivors may experience infertility after breast cancer due to chemotherapy-related gonadotoxicity and the delay in childbearing required when women are taking hormonal therapy. Fertility outcomes among breast cancer survivors are discussed elsewhere. (See "Overview of infertility and pregnancy outcome in cancer survivors" and "Fertility and reproductive hormone preservation: Overview of care prior to gonadotoxic therapy or surgery".)

Cancer outcomes and recommendations regarding timing of attempted pregnancy are discussed here:

●We typically advise women to wait for at least two years from the time of the diagnosis before attempting pregnancy [91-93]. The primary reason for this approach is to see that the patient does not have early cancer recurrence. Some data suggest that pregnancy sooner than two years is safe [94-96].

•Patients with hormone receptor-positive breast cancer are treated with adjuvant hormone therapy. A recent study found that temporary interruption of adjuvant endocrine therapy does not confer a greater risk of breast cancer risk in the short term [97], but longer term data are required.

•The study examined cancer recurrence rates among 516 patients desiring pregnancy who had received adjuvant endocrine therapy for 18 to 30 months for stage I to III breast cancer [97]. The duration of interruption of endocrine therapy could be up to two years to allow for attempting pregnancy, delivery, and breastfeeding. The median time from cancer diagnosis to study enrollment was 29 months. Most patients (94 percent) had stage I or II disease. At a median follow-up of 41 months:

-Seventy-four percent had at least one pregnancy and 64 percent had at least one live birth.

-The three-year incidence of breast cancer events was 8.9 percent in patients in this study versus 9.2 percent in an external control cohort of patients who would have met entry criteria but did not interrupt endocrine treatment for pregnancy.

-Half of patients had resumed therapy within 26 months after treatment interruption.

Reassuringly, prior breast cancer treatments do not appear to increase the risk of congenital malformation [98].

●However, due to risks for teratogenicity, we encourage women with a history of hormone receptor-positive breast cancer to wait at least three months from cessation of tamoxifen (with or without ovarian suppression medication or an aromatase inhibitor and ovarian suppression medication, by extrapolation) before attempting pregnancy. (See "Gestational breast cancer: Treatment", section on 'Endocrine therapy'.)

●Women who were treated with trastuzumab for a human epidermal growth factor receptor 2 (HER2)-positive breast cancer should utilize effective contraception for at least seven months after the end of trastuzumab before attempting pregnancy because of trastuzumab-related oligohydramnios to the fetus, which could result in pulmonary hypoplasia and neonatal death. These data and other prescribing information are discussed separately. (See "Adjuvant systemic therapy for HER2-positive breast cancer", section on 'Prescribing information and formulations'.)

For women with a history of breast cancer, a subsequent pregnancy does not appear to compromise survival [94,99-102]. In a systematic review of 36 studies including over 112,000 patients with breast cancer, of whom 7505 had subsequent pregnancy, those with a pregnancy had better disease-free survival (HR 0.66) and overall survival (0.56) than those without pregnancy, trends that persisted even after correcting for potential confounders, including patient, tumor, treatment characteristics, and timing of pregnancy [103]. Similar results were observed in a 2011 retrospective analysis of 14 case-control studies [99]. The improved cancer outcomes are likely explained by a selection bias known as the "healthy mother effect," such that only healthy breast cancer survivors were able to conceive and carry a pregnancy [96].

In addition, a case-control study suggests that pregnancy after breast cancer is safe regardless of estrogen receptor status [102].

Similar data now exist for women who are breast cancer susceptibility gene (BRCA) carriers with a history of breast cancer, and we offer similar counseling. Retrospective cohort studies of such women showed that pregnancy was not associated with increased risks of breast cancer recurrence or pregnancy complications [104,105].

Contraception after breast cancer — The World Health Organization guidelines for medical eligibility for contraceptive use have recommended avoiding hormonal contraception in women with a current or past history of breast cancer (particularly in those with hormone receptor-positive disease) (table 4). Although this is our typical practice, we do make exceptions to this approach. Specifically, although we first suggest use of a nonhormonal contraceptive method (condom, diaphragm, copper intrauterine device [IUD]), some patients may reasonably opt for a low-dose levonorgestrel-releasing contraception device (LNG-IUD), either for contraception or endometrial protection on tamoxifen. Patients with a low risk of recurrence, double mastectomy, or remote history of cancer may be appropriate candidates for this option, depending on their values and preferences. If a patient is interested in an LNG-IUD, we discuss that the systemic absorption of hormone is likely to be low, although the safety and efficacy of such an approach has not been well validated. (See "Contraception: Counseling and selection", section on 'Special populations'.)

The reason for the limitations in available data is that women with breast cancer have traditionally been excluded from studies of hormonal contraceptives. The LNG-IUD has been evaluated in women with a history of breast cancer, although primarily as a method of endometrial protection from the effects of tamoxifen rather than as a contraceptive modality. Data are limited and inconclusive. For example, one retrospective cohort study of breast cancer survivors suggested an increased risk of recurrence among cases (LNG-IUD users, n = 79) over controls (those who did not use LNG-IUD, n = 120) [106]. The rate of breast cancer recurrence was higher in cases compared with matched controls (22 versus 17 percent; odds ratio [OR] 1.86, 95% CI 0.86-4.00), although the difference was not statistically significant. However, other data suggest that progesterone-eluting IUDs may be safe and prevent endometrial pathology in premenopausal women on tamoxifen [107]. (See "Managing the side effects of tamoxifen and aromatase inhibitors", section on 'Tamoxifen'.)

CARDIOMETABOLIC ISSUES — Patients who have been treated for breast cancer are at risk for cardiometabolic effects [108,109], including hypertension, diabetes, and dyslipidemia. Routine screening and follow-up for these issues in the primary care setting is appropriate. (See "Clinical manifestations, diagnosis, and treatment of anthracycline-induced cardiotoxicity" and "Cardiotoxicity of trastuzumab and other HER2-targeted agents" and "Cardiotoxicity of radiation therapy for breast cancer and other malignancies".)

In one study including almost 15,000 patients with newly diagnosed breast cancer and 75,000 matched controls, breast cancer patients had a higher incidence of hypertension (10.9 versus 8.9 percent) and diabetes (2.1 versus 1.7 percent) after two years, with higher diabetes incidence persisting after ten years (9.3 versus 8.8 percent); risk of hyperlipidemia was not increased [108]. Although this study was conducted in an integrated health care delivery system and adjusted for primary care utilization prior to diagnosis, surveillance bias must be considered (breast cancer survivors are seen more frequently in the health care system, as part of routine surveillance).

QUALITY OF LIFE — Quality of life is a multidimensional construct that takes into account the physical, mental, social, economic, and spiritual aspects of life. Limited data suggest that patients treated for breast cancer have good quality of life, particularly as they move beyond the treatment period [4,13,110,111]. However, they may continue to have some lingering concerns. For example, in one study that included over 280 long-term survivors (without evidence of a recurrence >7 years) compared with almost 170 controls (without a history of breast cancer), self-reported deficits appeared to be limited to issues related to cognitive functioning and finances [110]. Young women (age <40 years at diagnosis) may be particularly at risk for decline in quality of life after breast cancer, and attention to their life stage-related concerns (including fertility as well as psychosocial issues) is warranted in follow-up [112].

Multiple studies have shown that exercise improves quality of life in breast cancer survivors. Therefore, patients should be encouraged to adopt a physically active lifestyle following treatment for breast cancer. Further discussion on the role of physical activity in breast cancer survivors is discussed separately. (See "The roles of diet, physical activity, and body weight in cancer survivors".)

COORDINATION OF CARE — If agreed upon by the patient, the treating oncologist, and the primary care physician (PCP), shared care would provide treatment summary information and a plan for follow-up care to both the patient and the PCP. The level of shared follow-up by the oncology specialist and PCP could depend upon patient and provider preferences. Communication between the PCP and subspecialist is vital given that uncertainties about clinician roles and responsibilities can lead to deficiencies in care [4]. (See "Overview of cancer survivorship care for primary care and oncology providers", section on 'Coordination of care' and "Assuring quality of care for cancer survivors: The survivorship care plan".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Breast cancer".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Lymphedema after cancer surgery (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Introduction – Essential elements of management for breast cancer survivors who have completed active treatment and have no evidence of disease are cancer surveillance, encouragement of adherence with ongoing treatment and lifestyle recommendations, treatment of medical and psychosocial consequences of cancer and its therapy, and care coordination between specialists and primary care providers (PCPs). (See 'Introduction' above.)

●Components of follow-up and counseling

•Survivor follow-up should include updated history, regular physical examination, and breast imaging (ie, mammography). The follow-up should not only focus on cancer surveillance, but also on any late-treatment-related complications, psychosocial issues, and occupational problems. (See 'Components of follow-up' above.)

•All women with breast cancer should be counseled about the role of genetic testing and counseling. (See 'Genetic counseling' above.)

•Laboratory studies or radiologic imaging to screen for distant recurrence in asymptomatic patients should not be performed. (See 'Role of laboratory evaluation and other imaging' above.)

•All breast cancer survivors should pursue a healthy lifestyle that includes following a prudent diet, pursuing or maintaining an active exercise program, minimizing alcohol intake, and refraining from smoking. (See 'Promoting a healthy lifestyle' above.)

●Reproductive issues – Although data are limited, studies do not indicate an increased risk of recurrence for survivors who become pregnant or have an impact on pregnancy outcomes. (See 'Reproductive issues' above.)

•We typically advise women to wait for at least two years from diagnosis before attempting pregnancy.

•For women with breast cancer who wish to prevent pregnancy, we suggest not administering hormonal contraception (Grade 2C). Although this is our typical practice, we do make exceptions to this approach. Specifically, although we first suggest use of a nonhormonal contraceptive method (condom, diaphragm, copper intrauterine device [IUD]), some patients may reasonably opt for a low-dose levonorgestrel-releasing contraception device (LNG-IUD), either for contraception or endometrial protection on tamoxifen. Clinicians should counsel women about methods most consistent with their lifestyles and beliefs. (See 'Contraception after breast cancer' above.)

●Coordination of care – A variety of clinicians may adequately follow women after their primary therapy for breast cancer. Clinicians should be experienced in the surveillance of these patients, the complications that may arise from treatment, and breast examination, including the examination of irradiated breasts. A shared care model that integrates both specialists and PCPs in ongoing follow-up care may provide the best adherence to guidelines for recommended care, but communication and coordination of care is required. (See 'Coordination of care' above.)