Abstract
Owing to improvements in screening and adjuvant therapy, survival following the diagnosis of breast cancer has improved markedly over the past three decades. This chapter will focus on MD Anderson’s recommendations for surveillance and treatment in breast cancer survivors. Because randomized trials have not demonstrated a survival benefit with intensive monitoring, current guidelines support the use of medical history review, physical examination, and annual mammograms as the bedrock of breast cancer surveillance. In addition, given the multidisciplinary approach to breast cancer treatment and surveillance, it is essential to monitor for and treat long-term effects of breast cancer treatment, including lymphedema, cardiac toxicity, ovarian failure, bone disorders, and secondary malignancies.
Access provided by Autonomous University of Puebla. Download chapter PDF
Similar content being viewed by others
Keywords
- Breast Cancer
- Acute Myeloid Leukemia
- Breast Cancer Survivor
- Aromatase Inhibitor
- National Comprehensive Cancer Network
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
FormalPara Chapter OverviewOwing to improvements in screening and adjuvant therapy, survival following the diagnosis of breast cancer has improved markedly over the past three decades. This chapter will focus on MD Anderson’s recommendations for surveillance and treatment in breast cancer survivors. Because randomized trials have not demonstrated a survival benefit with intensive monitoring, current guidelines support the use of medical history review, physical examination, and annual mammograms as the bedrock of breast cancer surveillance. In addition, given the multidisciplinary approach to breast cancer treatment and surveillance, it is essential to monitor for and treat long-term effects of breast cancer treatment, including lymphedema, cardiac toxicity, ovarian failure, bone disorders, and secondary malignancies.
Introduction
Owing to improvements in screening and adjuvant therapy, survival following the diagnosis of breast cancer has improved markedly over the past three decades (Berry et al. 2005). As a result, an increasing number of breast cancer survivors are requiring evaluation and treatment after the diagnosis of breast cancer. This chapter will focus on MD Anderson’s recommendations for surveillance and treatment in breast cancer survivors.
Surveillance
Type of Monitoring
A great concern for breast cancer survivors is the need for close monitoring for recurrent or metastatic disease. However, two large Italian trials, involving an aggregate of more than 2,500 patients with breast cancer, found no improvement in overall survival in patients who underwent intensive surveillance, including physical examination, mammogram, and rigorous tests such as bone scans and chest x-rays, compared with patients who received routine physical examinations and mammograms only (GIVIO Investigators 1994). As a result, current National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), and MD Anderson guidelines support surveillance of breast cancer survivors with physical examinations and mammograms; the use of more intensive monitoring is not recommended (see survivorship algorithms for invasive and noninvasive breast cancer, presented at the end of this chapter).
Interval for Monitoring
ASCO recommends that patients undergo a medical history review and physical examination every 3–6 months for the first 3 years following completion of primary therapy; this interval increases to 6–12 months at years 4 and 5 (Khatcheressian et al. 2006). After year 5, patients should undergo the medical history review and physical examination annually, unless earlier evaluation is clinically warranted. NCCN guidelines recommend similar intervals. The surveillance interval pattern used at MD Anderson is similar to that of the ASCO and NCCN guidelines; patients undergo a medical history review and physical examination every 3–6 months for 3 years, every 6–12 months for the next 2 years, and then annually after year 5.
History and Physical Examination
The medical history review and physical examination serve as the primary mechanism for detection of breast cancer recurrence (Lu et al. 2011). The medical history review should include questions that facilitate the detection of local recurrence or metastatic disease, covering the following:
-
Lumps, nodules, fullness, or skin changes (to detect local recurrence)
-
Persistent or worsening bone pain (to detect bone metastases)
-
Abdominal pain, increased abdominal girth, anorexia, or jaundice (to detect liver metastases)
-
Persistent cough, pleuritic chest pain, or shortness of breath (to detect pulmonary metastases)
-
New onset or worsening headache, visual changes, nausea, vomiting, dizziness, weakness, bowel or bladder incontinence, or changes in sensation (to detect metastases in the brain or spinal cord)
-
Changes in bowel habits or alteration in consistency or color of the stool (to detect gastrointestinal metastases)
-
Pelvic pain or discomfort or new-onset vaginal bleeding or spotting (to detect genitourinary metastases)
Physical examination should involve a complete examination of the patient from head to toe, including a neurologic examination, cardiac examination, pulmonary examination, abdominal evaluation, and evaluation of the breasts and lymph node basins.
Breast Imaging
Mammography remains the primary imaging technique for breast cancer, because it is the only imaging method that has consistently been found to reduce breast cancer–related mortality (Tabar et al. 2001). MD Anderson recommends obtaining a mammogram of a breast treated with breast-conserving therapy after 6 months, and then obtaining a bilateral mammogram annually. For patients who have undergone mastectomy, a mammogram of the contralateral breast should be obtained annually. For patients who have undergone mastectomy and reconstruction, a mammogram is not obtained for the reconstructed breast because mammography of the reconstructed breast has not been shown to increase detection of local recurrence (Fajardo et al. 1993).
Ultrasound is not currently recommended as a primary imaging technique for breast cancer. Instead, it is primarily used as an adjunct to mammography to further evaluate architectural distortion detected by the mammogram, distinguish between a solid mass and a cyst, and assist in localization of a mass or nodule to facilitate biopsy.
The use of magnetic resonance imaging (MRI) of the breast is also increasing. MRI has been found to have greater sensitivity for detection of breast malignancies than mammography, but no current evidence indicates that use of breast MRI improves outcomes when used as a breast surveillance technique (Kuhl et al. 2005). Thus, breast MRI is not routinely recommended for breast cancer surveillance, although it may be used as an adjunct to mammography in patients who have unique characteristics, such as BRCA1/2 mutation carrier status.
Screening for Second Primary Breast Cancers
Breast cancer survivors have a markedly higher risk of developing a second primary breast cancer, compared with the risk of developing primary breast cancer in the general population (Chaudary et al. 1984). Techniques for monitoring for a second primary breast cancer include mammography, ultrasonography, and MRI, as previously described.
Late Effects of Treatment
Surgery and Lymphedema
Mastectomy and axillary lymph node dissection increase the risk of developing lymphedema, which is associated with limb discomfort and decreased quality of life (Beaulac et al. 2002). Furthermore, chronic massive lymphedema may lead to Stewart-Treves syndrome, a rare disease that is associated with the development of lymphangiosarcoma of the involved extremity (Cozen et al. 1999). More commonly, lymphedema of the arm increases the likelihood of skin infections, such as cellulitis, for which close monitoring should be performed.
Chemotherapy
Cardiac Toxicity
Compared with first-generation regimens such as CMF (cyclophosphamide, methotrexate, and 5-fluorouracil), treatment with anthracyclines has been associated with a significant reduction in breast cancer–related mortality and overall mortality (Early Breast Cancer Trialists’ Collaborative Group 2012). However, anthracycline use increases the risk of congestive heart failure in a dose-dependent fashion (Bristow et al. 1981). The risk of anthracycline-related cardiomyopathy increases with age, combination with trastuzumab, and combination with mediastinal radiation therapy (Pinder et al. 2007).
In contrast with anthracycline-related cardiomyopathy, trastuzumab-related cardiotoxicity is often reversible with treatment discontinuation and is not dose-dependent (Keefe 2002). Most often, trastuzumab-related cardiomyopathy is detected by echocardiogram or multigated acquisition scan and is not clinically apparent at the time of diagnosis. Monitoring for cardiac complications from each regimen requires a multidisciplinary approach, with input from each patient’s primary care physician, oncologist, and cardiologist.
Neurologic Toxicity
Review of cross-sectional cognitive outcome studies reveals that the prevalence of chemotherapy-associated cognitive decline ranges from 17% to 75% (Correa and Ahles 2008). Prospective studies of breast cancer survivors undergoing chemotherapy have generated conflicting results, with some studies noting a significant decline in cognitive function and others finding no difference compared with baseline (Wefel et al. 2004b; Shilling et al. 2005; Bender et al. 2006; Hurria et al. 2006; Jenkins et al. 2006; Stewart et al. 2008; Quesnel et al. 2009). However, the patient’s self-perceived cognitive dysfunction is integrally linked to increased psychological distress (Wefel et al. 2004a). Boykoff et al. (2009) published compelling qualitative evidence of the negative effects of “chemobrain” on the economic, emotional, and interpersonal aspects of breast cancer survivors’ lives. Furthermore, a recent prospective study of 101 patients with breast cancer noted that self-perceived cognitive dysfunction was significantly related to negative affectivity (p = .015) and depression (p < .001; Hermelink et al. 2010). Thus, even in the setting of cancer “cure” following chemotherapy, breast cancer survivors continue to face the critical barrier of worsened cognition and its downstream emotional distress in their daily lives.
Ovarian Failure
The risk of chemotherapy-related ovarian failure is related to the dose and type of chemotherapy and the age at diagnosis (Goodwin et al. 1999). Specifically, risk of ovarian failure is markedly increased when the chemotherapy regimen includes cyclophosphamide or anthracycline and is administered to women older than 35 years. Patients with breast cancer may experience hot flashes, vaginal dryness, and mood changes. Early evaluation and symptomatic treatment is essential to facilitate improved quality of life. Furthermore, early ovarian failure increases the risk of osteopenia or osteoporosis, for which close monitoring should occur. Treatment with calcium, vitamin D, and bisphosphonates may be necessary to maintain adequate bone health in this setting (Hillner et al. 2003; see algorithm for breast cancer survivorship bone health, presented at the end of this chapter).
Second Malignancies
Research from our institution has demonstrated a small increased risk of acute myeloid leukemia after adjuvant chemotherapy (1.8% vs 1.2%) in women older than 65 years (Patt et al. 2007). Use of more intense regimens that included two or more cycles containing 2,400 mg/m2 cyclophosphamide with granulocyte colony-stimulating factor support resulted in a cumulative incidence of acute myeloid leukemia of 1.01% (95% confidence interval, 0.63–1.62%), compared with 0.21% (95% confidence interval, 0.11–0.41%) for patients treated with standard AC (doxorubicin and cyclophosphamide) regimens (Smith et al. 2003). Although the benefit from adjuvant chemotherapy exceeds the risk of developing acute myeloid leukemia, appropriate understanding of this risk is necessary for long-term follow-up.
Radiation Therapy
Cardiovascular Toxicity
Historically, postmastectomy radiation was found to increase the risk of cardiovascular toxicity. A large retrospective study of breast cancer survivors demonstrated a significant increase in overall mortality rates in patients who had received postmastectomy radiation; this effect was attributed to deaths from cardiovascular disease (Jones and Ribeiro 1989). However, with advances in radiation therapy and development of adaptive techniques to reduce cardiac exposure to radiation, recent randomized trials evaluating patients who received postmastectomy radiation therapy have shown no increase in cardiovascular morbidity (Hojris et al. 1999). But even with modern radiation therapy techniques, careful monitoring for symptoms of cardiac toxicity remains essential during follow-up visits.
Second Malignancies
Although they are rare, secondary malignancies are a potential late effect of radiation for the treatment of breast cancer. A retrospective study of the Surveillance, Epidemiology, and End Results (SEER) Cancer Incidence Database demonstrated that, at 15 years after diagnosis of breast cancer, the cumulative incidence of angiosarcoma was 0.9 per 1,000 patients who had received radiation therapy, compared with 0.1 per 1,000 patients who had not received radiation therapy (Yap et al. 2002). In patients who have received radiation therapy, an angiosarcoma presents in the irradiated field as a purple macule or papule; clinical suspicion of malignancy should lead to immediate core biopsy for further assessment. In addition to risk of solid tumor malignancies such as angiosarcoma, risk of hematologic malignancies such as acute myeloid leukemia and myelodysplastic syndrome is also slightly increased following radiation therapy (Kaplan et al. 2011).
Furthermore, data from the SEER database have demonstrated that, at 10 years after the breast cancer diagnosis, patients who had received radiation therapy had a relative risk of 2.0 for developing lung cancer, compared with patients who had not received radiation therapy (Neugut et al. 1993). This risk affected all three major subtypes of breast cancer: small cell, squamous cell, and adenocarcinoma. Similar risks for esophageal cancer were observed with older radiation techniques; these risks have declined with the implementation of new radiation techniques that enable greater exclusion of the esophagus from the irradiated field (Levi et al. 2005).
The risk of developing contralateral breast cancer is also slightly increased with older radiation therapy techniques; the Early Breast Cancer Trialists’ Collaborative Group found a significantly increased incidence of contralateral breast cancer (rate ratio, 1.18) in patients who had received radiation therapy (Clarke et al. 2005). A more recent study found that patients younger than 45 years, particularly those with strong family histories, appeared to have an increased risk of developing contralateral breast cancer following postmastectomy radiation therapy (Hooning et al. 2008).
Hormonal Therapy
Tamoxifen
Although tamoxifen has been shown to reduce the risk of recurrence of early-stage breast cancer, it acts as a selective estrogen receptor modulator and may increase the risk of endometrial carcinoma and uterine sarcomas. Careful monitoring of each patient with an intact uterus who has taken or is taking tamoxifen is therefore essential. Tamoxifen also increases the risk of deep venous thrombosis, and patients should be educated regarding the signs and symptoms of deep venous thrombosis. Furthermore, because tamoxifen is associated with ocular toxicity (although rarely), patients should be counseled to maintain close follow-up with their ophthalmologist.
Aromatase Inhibitors
The ATAC (anastrozole, tamoxifen, alone or in combination) trial demonstrated that anastrozole, compared with tamoxifen, reduced the risk of recurrence of early-stage breast cancer (Cuzick et al. 2010). As a result, aromatase inhibitors have become the standard of care for the treatment of hormone receptor-positive breast cancer in postmenopausal woman. However, although aromatase inhibitors have a favorable side effect profile compared with tamoxifen, they have a negative effect on bone health through estrogen deprivation (Eastell et al. 2011). As a result, patients should undergo regular monitoring with bone density studies and receive counseling regarding bone health to reduce their risk of developing worsening osteopenia or osteoporosis.
Psychosocial Functioning
An important aspect of follow-up with breast cancer survivors is the true acknowledgment of the grief and sadness that is associated with the loss of all or part of the female breast. Furthermore, following treatment, many patients enter into to a period of increased anxiety, depression, and stress (Khan et al. 2012). Many patients may benefit from participation in breast cancer support groups, particularly those that are geared toward their specific demographic. For example, young breast cancer survivors often gravitate to the Young Survival Coalition, which focuses on meeting the needs of young women who have been diagnosed with breast cancer. The Sisters Network provides strength and support to young and old African-American women who are breast cancer survivors. In addition, many breast cancer survivors find benefit in individual counseling sessions, which may focus on mindfulness and meditation to reduce fears of recurrence (Tacon 2011).
Key Practice Points
-
Current guidelines support surveillance of breast cancer survivors with a physical examination and a mammogram; use of more intensive monitoring is not recommended.
-
Mammography remains the primary imaging technique for breast cancer because it is the only imaging method that has consistently been found to reduce breast cancer–related mortality.
-
Risk of anthracycline-related cardiomyopathy increases with age, combination with trastuzumab, and combination with mediastinal radiation therapy.
-
Risk of ovarian failure is increased when the chemotherapy regimen includes cyclophosphamide or anthracycline and is administered to women older than 35 years.
-
Tamoxifen may increase the risk of endometrial carcinoma, uterine sarcoma, deep venous thrombosis, and ocular toxicity.
-
Patients who are treated with aromatase inhibitors should undergo regular monitoring with bone density studies and receive counseling regarding bone health to reduce their risk of developing worsening osteopenia or osteoporosis.
Suggested Readings
Beaulac SM, McNair LA, Scott TE, et al. Lymphedema and quality of life in survivors of early-stage breast cancer. Arch Surg 2002;137:1253–1257.
Bender CM, Sereika SM, Berga SL, et al. Cognitive impairment associated with adjuvant therapy in breast cancer. Psychooncology 2006;15:422–430.
Berry DA, Cronin KA, Plevritis SK, et al. Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med 2005;353:1784–1792.
Boykoff N, Moieni M, Subramanian SK. Confronting chemobrain: an in-depth look at survivors’ reports of impact on work, social networks, and health care response. J Cancer Surviv 2009;3:223–232.
Bristow MR, Mason JW, Billingham M, et al. Dose-effect and structure-function relationships in doxorubicin cardiomyopathy. Am Heart J 1981;102:709–718.
Chaudary MA, Millis RR, Hoskins EO, et al. Bilateral primary breast cancer: a prospective study of disease incidence. Br J Surg 1984;71:711–714.
Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;366:2087–2106.
Correa DD, Ahles TA. Neurocognitive changes in cancer survivors. Cancer J 2008;14:396–400.
Cozen W, Bernstein L, Wang F, et al. The risk of angiosarcoma following primary breast cancer. Br J Cancer 1999;81:532–536.
Cuzick J, Sestak I, Baum M, et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol 2010;11:1135–1141.
Early Breast Cancer Trialists’ Collaborative Group. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 2012;379:432–444.
Eastell R, Adams J, Clack G, et al. Long-term effects of anastrozole on bone mineral density: 7-year results from the ATAC trial. Ann Oncol 2011;22:857–862.
Fajardo LL, Roberts CC, Hunt KR. Mammographic surveillance of breast cancer patients: should the mastectomy site be imaged? Am J Roentgenol 1993;161:953–955.
GIVIO Investigators. Impact of follow-up testing on survival and health-related quality of life in breast cancer patients. A multicenter randomized controlled trial. JAMA 1994;271:1587–1592.
Goodwin PJ, Ennis M, Pritchard KI, et al. Risk of menopause during the first year after breast cancer diagnosis. J Clin Oncol 1999;17:2365–2370.
Hermelink K, Kuchenhoff H, Untch M, et al. Two different sides of “chemobrain”: determinants and nondeterminants of self-perceived cognitive dysfunction in a prospective, randomized, multicenter study. Psychooncology 2010;19:1321–1328.
Hillner BE, Ingle JN, Chlebowski RT, et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 2003;21:4042–4057.
Hojris I, Overgaard M, Christensen JJ, et al. Morbidity and mortality of ischaemic heart disease in high-risk breast-cancer patients after adjuvant postmastectomy systemic treatment with or without radiotherapy: analysis of DBCG 82b and 82c randomised trials. Radiotherapy Committee of the Danish Breast Cancer Cooperative Group. Lancet 1999;354:1425–1430.
Hooning MJ, Aleman BM, Hauptmann M, et al. Roles of radiotherapy and chemotherapy in the development of contralateral breast cancer. J Clin Oncol 2008;26:5561–5568.
Hurria A, Rosen C, Hudis C, et al. Cognitive function of older patients receiving adjuvant chemotherapy for breast cancer: a pilot prospective longitudinal study. J Am Geriatr Soc 2006;54:925–931.
Jenkins V, Shilling V, Deutsch G, et al. A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer. Br J Cancer 2006;94:828–834.
Jones JM, Ribeiro GG. Mortality patterns over 34 years of breast cancer patients in a clinical trial of post-operative radiotherapy. Clin Radiol 1989;40:204–208.
Kaplan HG, Malmgren JA, Atwood MK. Increased incidence of myelodysplastic syndrome and acute myeloid leukemia following breast cancer treatment with radiation alone or combined with chemotherapy: a registry cohort analysis 1990–2005. BMC Cancer 2011;11:260.
Keefe DL. Trastuzumab-associated cardiotoxicity. Cancer 2002;95:1592–1600.
Khan F, Amatya B, Pallant JF, et al. Factors associated with long-term functional outcomes and psychological sequelae in women after breast cancer. Breast 2012;21:314–320.
Khatcheressian JL, Wolff AC, Smith TJ, et al. American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol 2006;24:5091–2097.
Kuhl CK, Schrading S, Leutner CC, et al. Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer. J Clin Oncol 2005;23:8469–8476.
Levi F, Randimbison L, Te VC, et al. Increased risk of esophageal cancer after breast cancer. Ann Oncol 2005;16:1829–1831.
Lu W, de Bock GH, Schaapveld M, et al. The value of routine physical examination in the follow up of women with a history of early breast cancer. Eur J Cancer 2011;47:676–682.
Neugut AI, Robinson E, Lee WC, et al. Lung cancer after radiation therapy for breast cancer. Cancer 1993;71:3054–3057.
Patt DA, Duan Z, Fang S, et al. Acute myeloid leukemia after adjuvant breast cancer therapy in older women: understanding risk. J Clin Oncol 2007;25:3871–3876.
Pinder MC, Duan Z, Goodwin JS, et al. Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J Clin Oncol 2007;25:3808–3815.
Quesnel C, Savard J, Ivers H. Cognitive impairments associated with breast cancer treatments: results from a longitudinal study. Breast Cancer Res Treat 2009;116:113–123.
Shilling V, Jenkins V, Morris R, et al. The effects of adjuvant chemotherapy on cognition in women with breast cancer—preliminary results of an observational longitudinal study. Breast 2005;14:142–150.
Smith RE, Bryant J, DeCillis A, et al. Acute myeloid leukemia and myelodysplastic syndrome after doxorubicin-cyclophosphamide adjuvant therapy for operable breast cancer: the National Surgical Adjuvant Breast and Bowel Project experience. J Clin Oncol 2003;21:1195–1204.
Stewart A, Collins B, Mackenzie J, et al. The cognitive effects of adjuvant chemotherapy in early stage breast cancer: a prospective study. Psychooncology 2008;17:122–130.
Tabar L, Vitak B, Chen HH, et al. Beyond randomized controlled trials: organized mammographic screening substantially reduces breast carcinoma mortality. Cancer 2001;91:1724–1731.
Tacon AM. Mindfulness: existential, loss, and grief factors in women with breast cancer. J Psychosoc Oncol 2011;29:643–656.
Wefel JS, Lenzi R, Theriault R, et al. “Chemobrain” in breast carcinoma?: a prologue. Cancer 2004a;101:466–475.
Wefel JS, Lenzi R, Theriault RL, et al. The cognitive sequelae of standard-dose adjuvant chemotherapy in women with breast carcinoma: results of a prospective, randomized, longitudinal trial. Cancer 2004b;100:2292–2299.
Yap J, Chuba PJ, Thomas R, et al. Sarcoma as a second malignancy after treatment for breast cancer. Int J Radiat Oncol Biol Phys 2002;52:1231–1237.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Survivorship Algorithms
Survivorship Algorithms
These cancer survivorship algorithms have been specifically developed for MD Anderson using a multidisciplinary approach and taking into consideration circumstances particular to MD Anderson, including the following: MD Anderson’s specific patient population, MD Anderson’s services and structure, and MD Anderson’s clinical information. These algorithms are provided for informational purposes only and are not intended to replace the independent medical or professional judgment of physicians or other health care providers. Moreover, these algorithms should not be used to treat pregnant women.
Rights and permissions
Copyright information
© 2015 The University of Texas M. D. Anderson Cancer Center
About this chapter
Cite this chapter
Morrow, P.K. (2015). Breast Cancer Survivorship Management. In: Foxhall, L., Rodriguez, M. (eds) Advances in Cancer Survivorship Management. MD Anderson Cancer Care Series. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0986-5_5
Download citation
DOI: https://doi.org/10.1007/978-1-4939-0986-5_5
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4939-0985-8
Online ISBN: 978-1-4939-0986-5
eBook Packages: MedicineMedicine (R0)