Breast Cancer Follow-Up: Strategies for Successful Collaboration between Cancer Care Specialists and Primary Care Providers

Article Outline

• Abstract
• Introduction
• Primary Care Providers for Cancer Care Follow-Up
• Guidelines for Follow-Up
• Staging
  • Breast Cancer Survival Rates Vary by Stage
• Current Treatments and Potential Long-Term Side Effects
  • Surgery
  • Radiation Therapy
  • Chemotherapy
• Breast Cancer Chemotherapy Side Effects
  • Anthracyclines
  • Taxanes
  • Generalized Side Effects from Chemotherapy
  • Chemotherapy-Induced Menopause
• Biologic Therapy Side Effects
  • Trastuzumab Therapy
• Hormonal Therapy Side Effects
• Potential Emergencies in Patients with Breast Cancer
• Health Promotion
• Nutrition
• Emotional Considerations and Stress Management
• Conclusion
• References
• Uncited references
• Copyright

Abstract 

Nurse practitioners working in family or primary care often need to incorporate specialty care knowledge into their practice. Knowledge of breast cancer staging, treatment, common side effects, and possible long-term sequelae is critically important for primary care nurse practitioners caring for women with a history of breast cancer. The unique considerations of breast cancer staging, treatment, and long-term effects are reviewed in this article. The importance of optimal communication between the cancer care provider and the primary care providers is highlighted.

Keywords:  breast cancer , follow-up , long-term effects , recurrence , treatment

• 
  • View Large Image
  • Download to PowerPoint

Back to Article Outline

Introduction 

Nurse practitioners (NPs) working in family or primary care often need to incorporate specialty care knowledge into their practice. One important population of patients that requires specialty care knowledge is women with a history of breast cancer. The Fall 2008 Workforce Statement, issued by the American Society of Clinical Oncology (ASCO), urged the development of a workforce to ensure continuous delivery of high quality cancer care.¹ Restrategizing oncology care delivery through increasing the numbers and expanding the roles of NPs is considered critically important to meet current and potential future cancer care needs of the U.S. population.¹

Patient numbers are large. The American Cancer Society predicts that approximately 192,370 women will be diagnosed with breast cancer in 2009.² It is estimated that breast cancer will comprise 27% of all cancers.² Most women will survive breast cancer, leading to large numbers of women who will need their history of breast cancer diagnosis and treatment incorporated in their ongoing primary care. In 2008, more than 182,000 women were diagnosed with breast cancer, and 88% of those women will survive at least 5 years.³ After being treated with a combination of surgery and radiation or chemotherapy, these women often return to their primary care physicians for annual physicals, gynecologic examinations and management of other medical issues.⁴, ⁵, ⁶

Helping women transition from active treatment to survivorship care is a challenge that involves cancer care specialists and primary care physicians (PCPs).⁶ Important considerations that need to be communicated by the oncologic provider and understood by the primary NPs are follow-up testing requirements; the patient's stage of breast cancer and implications of recurrence; previous therapy and specific information regarding the diagnosis and management of long-term side effects; common emotional concerns associated with breast cancer diagnosis, treatment, and potential recurrence; and assessment and diagnosis of breast cancer oncologic emergencies. Priorities include having a working knowledge of the patient's breast cancer treatments, possible long-term implications of these treatments, clinical presentation of breast cancer recurrence or metastasis, and psychological or emotional issues that can result from breast cancer diagnosis and treatment. The primary care NP can use the information provided by the cancer care provider to complete a differential diagnosis inclusive of possible oncologic considerations and provide the patient with the appropriate diagnostic workup, treatment, or referral (Table 1).

Table 1. Patient Information Needed for Communication from the Cancer Center to the PCP

Back to Article Outline

Primary Care Providers for Cancer Care Follow-Up 

A study conducted by Mao et al.² examined breast cancer survivors' perceptions of PCP-related survivorship care. Results indicated that the areas of PCP-related care most strongly endorsed were general care, psychosocial support, and health promotion.² Despite the fact that breast cancer survivors perceived a high quality of general care provided by their PCPs, they were not as confident in their PCP's ability to deliver cancer-specific survivorship care. Fewer survivors perceived their PCPs as knowledgeable about cancer follow-up, late effects of cancer therapies, or treating symptoms related to cancer or cancer therapies.²

However, ASCO recommends tapering interactions with the cancer care providers and moving care to the primary care setting. Follow-up of a patient by multiple specialists after initial breast cancer therapy is costly, has not been shown to improve outcomes, and may represent a duplication of effort.⁷ Primary care follow-up for breast cancer survivors has been shown to be equal in critical outcomes of diagnosis of recurrent disease, anxiety, and health-related quality of life, compared to the follow-up care provided by breast cancer specialists in an oncology setting.⁴, ⁸

Back to Article Outline

Guidelines for Follow-Up 

Many breast cancer survivors request frequent radiographic and laboratory evaluation for breast cancer follow-up in order to determine if breast cancer has recurred. Radiographic and laboratory evaluation should be based on patient complaints rather than done routinely. This results in significant cost savings with equal patient outcomes.⁴, ⁸ No differences have been found in overall survival or disease-free survival rates between patients observed with intensive radiologic and laboratory testing and those observed with clinical visits and mammography.⁹, ¹⁰ Patients can be reassured that any patient complaint that is worrisome for recurrence or metastatic disease will be evaluated thoroughly with appropriate testing. Current ASCO guidelines recommend regular clinical evaluation in conjunction with annual mammography as the foundation of breast cancer follow-up care.⁷ The 2006 ASCO panel update⁷ recommends that all survivors have a careful history and physical examination every 3 to 6 months for the first 3 years after primary therapy, then every 6 to 12 months for the next 2 years, and then annually. Additionally, ASCO recommends that physicians counsel patients about the symptoms of recurrence, including new masses or skin nodules, bone pain, chest pain, dyspnea, abdominal pain, or persistent headaches.⁷ Routine evaluation of serum tumor markers is not recommended (Table 2).⁴ In November 2009, The U.S. Preventive Task Force¹¹ issued a recommendation statement questioning routine annual mammography in women between the ages of 40 and 49. This statement remains controversial. The decision to start regular, biennial screening mammography before the age of 50 years old should be an individual one and take into account patient context.¹¹ It is important to remind patients that these guidelines are for “healthy women” without a history of breast cancer. Annual mammography is still recommended for women with a history of breast cancer.

Table 2. Summary of Recommendations^*

When evaluating a woman with a history of early-stage breast cancer, the NP must first compile some basic information about the breast cancer diagnosis and treatment in order to evaluate the patient in view of her unique breast cancer experience. The staging of the disease as well as the history of current and past breast cancer treatment are important in the consideration of possible side effects and long-term complications that may impact the evaluation of a patient complaint in primary care.

Back to Article Outline

Staging 

The most widely used staging system for breast cancer is that of the American Joint Committee on Cancer (AJCC), which uses the TNM classification system.¹³ The TNM system is based on the description of the primary tumor (T), the status of regional lymph nodes (N), and the presence of distant metastases (M). This staging classification for breast cancer groups different patterns of breast, nodal, and distant tumor involvement into tumor stages that reflect prognosis.

Additional letters or numbers that appear after T, N, and M give more details about the tumor, lymph nodes, and metastasis.¹³ The letter T followed by a number from 0 to 4 describes the tumor's size and spread to the skin or to the chest wall under the breast. The letter N followed by a number from 0 to 3 indicates whether the cancer has spread to lymph nodes and, if so, how many lymph nodes are affected. The letter M followed by a 0 or 1 indicates whether the cancer has spread to distant organs. Once the T, N, and M categories have been determined, this information is combined in a process called stage grouping. There are five stages of breast cancer, stages 0, I, II, III, and IV.

Breast Cancer Survival Rates Vary by Stage 

The 5-year survival rate refers to the percentage of patients who live at least 5 years after being diagnosed with cancer. Five-year relative survival rates are a measure of net survival that is calculated by comparing overall survival with expected survival from a comparable set of people who do not have cancer (Table 3).¹³

Table 3. Breast Cancer Survival Rates By Stage

Back to Article Outline

Current Treatments and Potential Long-Term Side Effects 

Breast care specialists rank the detection of treatment-related morbidity the most important reason for follow-up care for women with breast cancer.⁷ The breast cancer survivor may have undergone multiple treatment modalities, including surgery, radiation, chemotherapy, biologic or targeted therapies, and/or endocrine therapy. Women may be receiving chronic breast cancer therapy such as trastuzumab and endocrine therapies. Not all patients receive all breast cancer therapies, but side effects for all the breast cancer treatment modalities can appear and persist.

Surgery 

Breast surgery is associated with side effects that include postsurgical pain, nausea, and fatigue. For women who have undergone surgery for breast cancer, long-term side effects may include pain, decreased mobility, and lymphedema in the arm of the affected side(s). The quality of pain experienced by the majority of women following any of the surgeries for breast cancer is most often described as relatively mild and is further described as “shooting,” “achiness,” “numbness,” or “an itch I can't scratch.” The decreased mobility experienced by some women can often be attributed to skin contractures of the axilla and chest wall.

Axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB) remains the standard of care in the management of invasive breast cancer.¹⁴, ¹⁵ Lymphedema, a side effect of breast and lymph node surgery, is caused by the interruption of the lymph system after the surgical removal of axillary lymph nodes (axillary dissection) for complete breast cancer staging. Lymphedema is the most common complication of ALND and can result in chronic and debilitating arm swelling. Although the reported incidence of lymphedema following breast cancer therapy varies widely across treatment modalities, approximately 1 in 4 to 5 women will develop arm edema after treatment of breast cancer. Radiotherapy to the dissected axilla doubles this risk.¹⁶, ¹⁷, ¹⁸, ¹⁹ Risk factors for lymphedema also include being overweight (body mass index of ≥25), axillary radiation, mastectomy, chemotherapy, cancerous lymph nodes, requirement of fluid aspiration after surgery, and active cancer status.¹⁹ In a study examining risk factors for lymphedema after breast cancer surgery, being overweight was identified as an important modifiable risk factor.¹⁹, ²⁰ Treatment for lymphedema is unfortunately somewhat limited; however, emphasizing meticulous skin care and physical therapy consultation for manual lymph drainage and/or exercise and compression garments may be utilized after breast cancer recurrence is definitively ruled out. It is extremely important that the NP not assume that all cases of lymphedema or pain following surgery are automatically related to long-term surgical side effects. Referral back to the surgeon is indicated for persistent pain or new onset of lymphedema.²¹

Radiation Therapy 

Long-term side effects from radiation therapy may include hyperpigmentation of the radiated skin, skin dryness, and soreness of the skin or ribs in the treated field, density of breast tissue, and/or areolar thickening.²², ²³ The dry, sore skin may further lead to axillary contractures, resulting in decreased flexibility. Some women develop radiation pneumonitis, an inflammation of the lung occurring anywhere from 2 weeks to 6 months after radiation therapy. Radiation pneumonitis can lead to permanent scarring of the lungs, known as radiation fibrosis, which is associated with more serious heart and lung problems.²², ²³ Although rare, secondary malignancies are a concern after radiation therapy.²², ²³

Chemotherapy 

Adjuvant or neoadjuvant chemotherapy refers to the use of chemotherapy as a systemic treatment before or after the tumor has been removed for the purpose of eradicating possible metastatic disease. The decision to utilize adjuvant chemotherapy is based on a number of factors, including the patient's age, size of the tumor, the presence of positive axillary lymph nodes, and medical comorbidities. While the primary care NP cannot be an expert in all chemotherapeutic regimens, an awareness of primary chemotherapy drugs used for breast cancer treatment and toxicity profile is necessary for appropriate follow-up care of women who have received these agents.

Back to Article Outline

Breast Cancer Chemotherapy Side Effects 

Anthracyclines 

Although not always used in early-stage breast cancer, anthracyclines have been the corner stone of breast cancer chemotherapy. The major long-term side effect of anthracylines is the slight risk (1%) of cardiomyopathy and congestive heart failure.²⁴, ²⁵ This risk is compounded if radiation therapy is administered directly to the chest wall.²⁶, ²⁷ Although the peak onset of symptomatic heart failure occurs 3 months after the last anthracycline dose, it also may take a decade to appear.²⁴ The optimum method and frequency of monitoring and predicting cardiotoxicity are as yet unknown. If the patient's baseline cardiac status is within normal limits, obtaining an electrocardiogram as part of a yearly physical may be all that is necessary. If there is a noted decline or change in cardiac status, referral to a cardiologist is required.²⁸

Taxanes 

The most common long-term side effect with taxane therapy is peripheral neuropathy, occurring in as many as 30% of patients.²⁹ These symptoms usually decrease slowly after cessation of therapy and rarely persist into a long-term complication. The residual neuropathies are not life threatening, but many patients report long-term impact on quality of life. After careful neurologic assessment, patients may initially be given pregabalin or gabapentin with mixed efficacy.³⁰ A referral to a neurologist may be necessary to evaluate nerve conduction damage.

Generalized Side Effects from Chemotherapy 

Cognitive disturbances are a potential long-term physiologic side effect of breast cancer therapy.³¹ Women will refer to memory loss or loss of executive function (higher-level thinking) as “chemo brain.” This popular lay term is a misnomer as it is not clear that all cognitive disturbances that result from breast cancer therapy are the result of chemotherapy only. There may be many other influences from the breast cancer experience that result in diminished cognitive function. Lack of standard cognitive function measurement and lack of pretreatment baseline measurement precludes an accurate assessment of incidence and prevalence.³² Although most symptoms resolve over time, the effect is sometimes long-term.³³ If cognition does not improve, a referral to a neuropsychological counselor may be necessary for formal evaluation and recommendations to address specific cognitive deficits.

Chemotherapy-Induced Menopause 

The effect of chemotherapeutic drugs on ovarian function varies greatly. The effects of chemotherapy on ovarian function are dependent on age (the higher the age the more likely is the loss of ovarian function), dose, and drug.³⁴, ³⁵ Currently, no known testing predicts the return of fertility in these women. The World Health Organization has defined menopause as the permanent cessation of menstruation resulting from loss of ovarian follicular activity.³⁶ Women must be cautioned that posttreatment menopause is confirmed by 1 year without menses and blood analysis confirming postmenopausal state. Without menses, a woman can become pregnant. Consequently, it is important to recommend contraception if a woman is unsure of her menopausal status.

Back to Article Outline

Biologic Therapy Side Effects 

Trastuzumab Therapy 

Biologic therapy agents target specific molecular pathways responsible for tumor growth. Approximately 15% to 30% of breast cancers overproduce a protein that accelerates cell growth. This growth-promoting protein, her-2/neu, makes tumors more likely to recur or metastasize.³⁷, ³⁸ A monocolonal antibody, trastuzumab targets the her-2/neu protein of breast tumors, essentially disabling the protein's growth producing abilities.³⁹ Women with early-stage cancers with her-2/neu-positive tumors will receive 1 year of trastuzumab treatment. There is limited toxicity with trastuzumab therapy. Cardiac toxicity has been reported for trastuzumab (2.6% without chemotherapy).⁴⁰ Cardiac monitoring through serial echocardiograms is usually done through the cancer care provider during the year of trastuzumab therapy.⁴¹ In contrast to anthracycline-induced cardiomyopathy, patients who have developed heart failure while undergoing trastuzumab therapy will regain heart function with the discontinuation of this medication. There are no specific guidelines for long-term cardiac monitoring in patients after the completion of trastuzumab therapy.

Back to Article Outline

Hormonal Therapy Side Effects 

Estrogen, a hormone produced by the ovaries, promotes the growth of some breast cancers. Women whose breast cancers test positive for estrogen receptors can be given antihormonal therapy to block the effects of estrogen on the growth of breast cancer cells. Tamoxifen, a selective estrogen receptor modulator, is the antiestrogen drug most commonly used.⁴², ⁴³, ⁴⁴, ⁴⁵, ⁴⁶ The symptom most commonly reported with tamoxifen is hot flashes. Pharmacologic and nonpharmacologic treatments are available for women who experience hot flashes. Many prospective randomized clinical trials have demonstrated the effectiveness of selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) family, such as venlafaxine, paroxetine, and sertaline to reduce hot flashes by as much as 50 to 60%.⁴⁷, ⁴⁸, ⁴⁹, ⁵⁰ In addition to SSRIs and SNRIs, gabapentin, a gamma-aminobutyric acid analog, has been evaluated for efficacy and safety, alone or in combination with an antidepressant such as venlafaxine or paroxetine.⁵¹, ⁵², ⁵³

Nonpharmacologic treatment for hot flashes is relatively common. It is estimated that 50 to 75% of postmenopausal women use alternative therapies for management of menopausal symptoms, and the prevalence may be even higher in women with breast cancer.⁵⁴, ⁵⁵ Interventions such as vitamin E, hypnosis, and acupuncture have been hypothesized to reduce and alleviate hot flashes, but studies have yet to determine strong efficacy.⁵⁶, ⁵⁷, ⁵⁸, ⁵⁹, ⁶⁰ For most nonpharmacologic therapies, safety and efficacy are not well established due to the limited number of well-designed complementary and alternative studies.

The most detrimental complication of tamoxifen therapy is an increase in the incidence of deep venous thrombosis and pulmonary embolism.⁴², ⁴³, ⁴⁴, ⁴⁵, ⁴⁶ Additional tamoxifen side effects include a slightly higher risk of uterine cancer and cataract development.⁶¹ NPs need to ensure that women taking tamoxifen have annual gynecologic and ophthalmologic examinations.

A class of drugs known as aromatase inhibitors (AIs) are used to treat postmenopausal women with both early- and late-stage hormone-sensitive breast tumors.⁴³, ⁶², ⁶⁴, ⁶⁵, ⁶⁶, ⁶⁷, ⁶⁸, ⁶⁹, ⁷⁰, ⁷¹, ⁷² These drugs are letrozole, anastrozole, and exemestane and have similar antitumor activity and toxicity profiles.⁶³ AIs work by blocking an enzyme responsible for producing small amounts of estrogen in postmenopausal women.

AIs are contraindicated in premenopausal women because AIs could promote an increase in ovarian production of estrogen, leading to higher estradiol levels. However, in certain instances, a premenopausal woman may receive an AI along with ovarian suppression via surgery, radiation, or medication. Menopause must be confirmed via the history of 1 year without menstrual periods and estradiol and follicular-stimulating hormones in the postmenopausal range. Recent clinical trials have demonstrated that AIs are more effective than tamoxifen at reducing breast cancer recurrences.⁶⁴, ⁶⁵, ⁶⁶, ⁶⁷, ⁶⁸, ⁶⁹, ⁷⁰

In postmenopausal women, antiestrogen drug therapies will be initiated before the patient leaves the cancer care provider and will generally continue for 5 years thereafter.⁷¹ The optimal duration of antiestrogen therapy for women with a history of early-stage breast cancer is currently 5 years, but longer periods of time may be beneficial.⁷¹ The continuation or discontinuation of these agents must be coordinated by the prescribing oncologist.

AIs are generally well tolerated.⁴³ Common side effects associated with antiestrogen therapy include hot flashes, myalgias and arthralgias, sleep disturbances, and weight gain.⁷³ It is often difficult to determine the exact etiology of these symptoms in light of the patient's prior treatment modalities. Management is largely symptomatic and beyond the scope of this article. If the side effects of the antiestrogen therapies are diminishing the patient's quality of life or prompting patient nonadherence, the patient needs to visit the cancer care provider for medication counseling.

Decrease in bone density is reported with AIs.⁴³, ⁷⁴, ⁷⁵ The initial assessment should include a detailed review of risk factors for osteoporosis, including a history of fragility fracture and a baseline bone mineral density (BMD) test. For postmenopausal women with normal BMD, dual energy x-ray absorptiometry scans are recommended once every 2 to 3 years.⁷⁵, ⁷⁶ More frequent monitoring may be appropriate in women transitioning to aromatase inhibitor treatment (i.e. annually).⁷⁵, ⁷⁶ BMD testing is recommended every 2 years with appropriate intervention as to degree of bone loss.⁷⁷ Patients with significant BMD loss upon follow-up, as well as those with a previous history of osteopenia or osteoporosis, should be referred to an endocrinologist for further evaluation.⁷⁵

Back to Article Outline

Potential Emergencies in Patients with Breast Cancer 

A woman with a history of early-stage breast cancer may present to a PCP with a manifestation of a new onset of advanced or metastatic cancer. Most often these presenting signs and symptoms can be evaluated in a timely fashion and the patient referred back to cancer care providers if a recurrence or metastatic disease is suspected. Rarely, however, will women present with an oncologic emergency. These emergencies need to be recognized and treated promptly in order to avoid possible dire patient outcomes (Table 4).⁷⁸, ⁷⁹, ⁸⁰, ⁸¹, ⁸², ⁸³, ⁸⁴, ⁸⁵, ⁸⁶

Table 4. Oncologic Emergencies in Breast Cancer

Back to Article Outline

Health Promotion 

There is no clear preventive intervention for reducing breast cancer recurrence. Some studies have examined the association between body weight, nutritional factors, physical activity, and the risk for primary breast cancer. However, relatively few studies have examined the association between these factors and the recurrence of disease and cure of the primary tumor.⁸⁷ Reduction in alcohol and intake of dietary fat, stress management, and weight loss, if postmenopausal and obese, as well as increasing physical activity, are some proactive measures that may be recommended.

Back to Article Outline

Nutrition 

Most estrogen circulating in postmenopausal women is produced in fat tissue.⁸⁸ Obesity is associated with an increased risk of breast cancer in postmenopausal women.⁸⁸, ⁸⁹, ⁹⁰ Several studies to date have examined the correlation between dietary fat and breast cancer, suggesting a relationship.⁹⁰, ⁹¹, ⁹², ⁹³ Studies of the influence of dietary fat intake have considered fat consumption in total calories from fat, different types of fat intake, and fat intake at specific times in the life cycle, for reducing the risk of both developing breast cancer and of recurrence after treatment for breast cancer.⁸⁸ Additionally, physical activity has been examined as a modifiable factor that may reduce the risk of recurrence and improve overall survival in breast cancer survivors. While several studies have examined the effect of physical activity on breast cancer, to date, findings have yet to fully support a protective effect of physical activity on breast cancer recurrence or mortality.⁸⁷, ⁹¹, ⁹⁴ The specific dietary guidelines to prevent breast cancer recurrence remain controversial. In the absence of specific guidelines with respect to nutrition and recurrence, NPs play an important role in advising all women to maintain a healthy lifestyle. Until further, more specific information is known, it is prudent for NPs to recommend a predominantly plant-based, low-fat diet with regular physical activity to limit fat consumption and maintain an optimal body weight.⁸⁷, ⁹⁰, ⁹³

Back to Article Outline

Emotional Considerations and Stress Management 

A breast cancer diagnosis bears an enormous emotional implication for the patient and her family.⁹⁶ In combination with body image changes from breast surgery and radiation, current or long-term side effects from treatment and estrogen deprivation, there can be overwhelming feelings of vulnerability and uncertainty related to the cancer diagnosis.⁹⁷ It is important that the NP understand the psychological burden that many patients experience. Some patients may be reluctant or unable to articulate their feelings. The primary care NP can empathetically inquire as to how a woman is coping emotionally, offer support, and be familiar with local breast cancer support resources. Nurses should be cautioned to screen patients for clinical depression, monitor patients who are already taking antidepressants, observe for antidepressant polypharmacy, and determine undertreatment of depression.

Back to Article Outline

Conclusion 

Parity in outcomes between primary and specialty care and emerging trends in healthcare delivery such as limitations in specialty care reimbursement and a decrease in the number of cancer care providers³ make it likely that the primary, a women's health, and the family NPs will be caring for breast cancer survivors. Consequently, NPs in primary care need to consider the implications of this potential new role.

Nurse practitioners have established evidence of cost-effectiveness, patient satisfaction, and quality care outcomes in multiple care settings.⁵, ⁶, ⁷, ⁸, ⁹, ¹⁰ With successful coordination, sharing of patient information from the cancer care provider, and an awareness of long-term breast cancer issues, NPs in primary care can provide optimal care for women with breast cancer.

Back to Article Outline

References 

1. American Society of Clinical Oncology  . ASCO Fall 2008 Workforce Statement . Available at: http://www.asco.org/asco/downloads/research%20policy/workforce%20page/asco%20workforce%20strategic%20plan.pdf Accessed September 10, 2009
   • View In Article
2. Mao JJ , Bowman MA , Stricker CT , et al.   Delivery of survivorship care by primary care physicians: The perspective of breast cancer patients . J Clin Oncol . 2009;27(6):933–938
   • View In Article
   • CrossRef
3. Jemal A , Siegel R , Ward E , et al.   Cancer statistics, 2008 . CA Cancer J Clin . 2008;58(2):71–96
   • View In Article
   • CrossRef
4. Grunfield E , Man D , Yudkin P , et al.   Routine follow up of breast cancer in primary care: Randomised trial . Br Med J . 1996;313(1):665–669
   • View In Article
5. Grunfeld E , Yudkin P , Adewuyl-Dalton R , et al.   Follow up in breast cancer: Quality of life unaffected by general practice follow up . Br Med J . 1995;311(1):54
   • View In Article
6. Grunfeld E , Levine MN , Julian JA , et al.   Randomized trial of long-term follow up for early stage breast cancer: A comparison of family physician versus specialist care . J Clin Oncol . 2006;24(1):848–855
   • View In Article
   • CrossRef
7. 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(1):5091–5097
   • View In Article
   • CrossRef
8. Loprinzini CL , Hayes D , Smith T . Doc, shouldn't we be getting some tests? . J Clin Oncol . 2000;18(1):2345–2348
   • View In Article
   • MEDLINE
9. The GIVIO Investigators  . Impact of follow up testing on survival and health related quality of life in breast controlled patients: A multicenter randomized controlled trial . JAMA . 1994;271(1):1587–1592
   • View In Article
   • MEDLINE
10. Rosselli Del Turco M , Palli D , Cariddi A , et al.   Intensive diagnostic follow up after treatment of primary breast cancer: A randomized trial—National Research Council Project on Breast Cancer Follow-Up . JAMA . 1994;271(1):1593–1597
    • View In Article
    • MEDLINE
11. U.S. Preventive Task Force  . Screening for breast cancer: U.S. preventive services task force recommendation statement . Ann Intern Med . 2009;151:716–726
    • View In Article
12. American Cancer Society  . How is breast cancer staged? . Available at: http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_breast_cancer_staged_5.asp? sitearea= Accessed September 20, 2009
    • View In Article
13. McMasters KM . The eternally enigmatic axilla: Further controversy about axillary lymph nodes in breast cancer . Ann Surg Oncol . 2004;10(1):1128–1130
    • View In Article
    • MEDLINE
    • CrossRef
14. Schwartz GF . Clinical practice guidelines for the use of axillary sentinel lymph node biopsy in carcinoma of the breast: Current update . Breast J . 2004;10(1):85–88
    • View In Article
    • MEDLINE
    • CrossRef
15. Edwards TL. Prevalence and aetiology of lymphoedema after breast cancer treatment in southern Tasmania. ANZ J Surg. 20(6):412-418.
    • View In Article
16. Erikson VS , Pearson ML , Ganz PA , et al.   Arm edema in breast cancer patients . J Natl Cancer Inst . 2001;93(1):96–111
    • View In Article
    • MEDLINE
    • CrossRef
17. Goffman TE, Laronga C, Wilson L, et al. Lymphedema of the arm and breast in irradiated breast cancer patients: Risks in an era of dramatically changing axillary surgery. Breast J. 10(5): 405-411.
    • View In Article
18. Swenson KK , Nissen MJ , Leach JW , et al.   Case control study to evaluate predictors of lymphedema after breast cancer surgery . Oncol Nurs Forum . 2009;36(2):185–193
    • View In Article
19. Johansson K , Ohlsson K , Ingvar C , et al.   Factors associated with the development of arm lymphedema following cancer treating: A match pair case-control study . Lymphology . 2002;35(2):59–71
    • View In Article
    • MEDLINE
20. Williams AF, Vadgama A, Franks PJ, et al. A randomized controlled crossover study of manual lymphatic drainage therapy in women with breast cancer-related lymphoedema. Eur J Cancer Care. 11(4): 254-261.
    • View In Article
21. American Cancer Society  . Possible side effects of radiation therapy . Available at: http://www.cancer.org/docroot/ETO/content/ETO_1_4X_Side_Effects_of_Radiation_Therapy.asp Accessed September 17, 2009
    • View In Article
22. National Cancer Institute  . Radiation therapy side effects . Available at: http://www.cancer.gov/cancertopics/radiation-therapy-and-you/page6 Accessed September 17, 2009
    • View In Article
23. Hershman DL . Anthracycline cardiotoxicity after breast cancer treatment . Oncology . 2009;23(3):
    • View In Article
24. Pinder MC , Zhigana D , Goodwin JS , et al.   Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer . J Clin Oncol . 2007;25(25):3808–3814
    • View In Article
    • CrossRef
25. Pfeffer B , Tziros C , Katz R . Current concepts of anthracycline cardiotoxicity: Pathogenesis, diagnosis and prevention . Br J Cardiol . 2009;16(2):85–89
    • View In Article
26. Wouters KA , Kremer LC , Miller TL , Herman EH , Lipshultz SE . Protecting against anthracycline-induced myocardial damage: a review of the most promising strategies . Br J Haematol . 2005;131:561–578
    • View In Article
    • MEDLINE
    • CrossRef
27. Roul G , Cohen C , Lieber A . Anthracycline-induced cardiomyopathy . Press Medicale . 2009;38(6):987–994
    • View In Article
28. Lee J , Swain S . Peripheral neuropathy induced by microtubule-stabilizing agents . J Clin Oncol . 2006;24(10):1633–1642
    • View In Article
    • CrossRef
29. Dworkin RH , Backonja M , Rowbotham MC , et al.   Advances in neuropathic pain:diagnosis, mechanisms, and treatment recommendations . Arch Neurol . 2003;60(11):1524–1534
    • View In Article
    • MEDLINE
    • CrossRef
30. Schagen SB , Van Dam FS , Muller MJ , et al.   Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma . Cancer . 1999;85(3):640–650
    • View In Article
    • MEDLINE
    • CrossRef
31. Vardy J , Rourke S , Tannock IF . Evaluation of cognitive function associated with chemotherapy: a review of published studies and recommendations for future research . J Clin Oncol . 2007;25(17):2455–2463
    • View In Article
    • CrossRef
32. Grunfeld E , Dhesy-Thind S , Levine M . Clinical practice guidelines for the care and treatment of breast cancer: follow-up after treatment for breast cancer (summary of the 2005 update) . CMAJ . 2005;172:1319
    • View In Article
    • CrossRef
33. Up To Date  . Ovarian Failure due to anticancer drugs and radiation . Available at: http://www.uptodate.com/patients/content/topic.do?topicKey=∼QTTQH1AMXyPAGQ#7 Accessed September 17, 2009
    • View In Article
34. Wallace WH , Thomson AB , Saran F , et al.   Predicting age of ovarian failure after radiation to a field that includes the ovaries . Int J Radiat Oncol Biol Phys . 2005;62(3):738–744
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (407 KB)
    • CrossRef
35. World Health Organization. Research on menopause in the 1990s. Technical report Scr. 866, Geneva, Switzerland; 1996.
    • View In Article
36. Menard S , Fortis S , Castiglioni F , et al.   HER2 as a prognostic factor in breast cancer . Oncology . 2001;61(Suppl 2):67–72
    • View In Article
    • CrossRef
37. Ross JS , Fletcher JA . The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy . Stem Cells . 1998;16:413–428
    • View In Article
    • MEDLINE
    • CrossRef
38. Emens LA , Davidson NE . Trastuzumab in breast cancer . Oncology (Williston Park) . 2004;18:1117–1128
    • View In Article
    • MEDLINE
39. Up To Date  . Cardiotoxicity of Trastuzumab . Available at: http://www.uptodate.com/patients/content/topic.do?topicKey=∼h4anaQIBOGXLHRa&selectedTitle=5∼71&source=search_result Accessed September 17, 2009
    • View In Article
40. Craft BS , Hortobagyi GN , Moulder SL . Adjuvant biologic therapy for breast cancer . Cancer J . 2007;13(3):156–161
    • View In Article
    • CrossRef
41. American Cancer Society  . Tamoxifen cancer.org BC Facts and Figures 2007-2008 . Available at: http://www.cancer.org/downloads/STT/BCFF-Final.pdf Accessed September 22, 2009
    • View In Article
42. Carlson RW , Hudis CA , Pritchard KI , et al.   Adjuvant endocrine therapy in hormone receptor-positive postmenopausal breast cancer: Evolution of NCCN, ASCO, and St Gallen recommendations . J Natl Compr Canc Netw . 2006;4(10):971–979
    • View In Article
    • MEDLINE
43. Carlson RW , Anderson BO , Burstein HJ , et al.   Breast cancer . J Natl Compr Canc Netw . 2005;3:228–289
    • View In Article
44. Winer EP , Hudis C , Burstein HJ , et al.   American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor positive breast cancer: status report 2004 . J Clin Oncol . 2003;21:3357–3365
    • View In Article
    • MEDLINE
    • CrossRef
45. Goldhirsch A , Glick JH , Gelber RD , et al.   Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005 . Ann Oncol . 2005;16:1569–3365
    • View In Article
    • MEDLINE
    • CrossRef
46. Sterns V . Serotonergic agents as an alternative to hormonal therapy for the treatment of menopausal vasomotor symptoms . Treat Endocrinol . 2006;5(2):83–87
    • View In Article
    • MEDLINE
    • CrossRef
47. Kimmick GG , Lovato J , McQuellon R , et al.   Randomized, double blind, placebo-controlled, crossover study of sertaline (Zoloft) for the treatment of hot flashes in women with early stage breast cancer taking tamoxifen . Breast J . 2006;12(2):114–122
    • View In Article
    • MEDLINE
    • CrossRef
48. Loprinzi CL , Sloan JA , Perez EA , et al.   Phase III evaluation of fluoxetine for treatment of hot flashes . J Clin Oncol . 2002;20(6):1578–1583
    • View In Article
    • MEDLINE
    • CrossRef
49. Loprinzi CL , Kugler JW , Sloan JA , et al.   Venlafaxine in management of hot flashes in survivors of breast cancer: A randomized controlled trial . Lancet . 2000;356(9247):2059–2063
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (91 KB)
    • CrossRef
50. Pandya KJ , Morrow GR , Roscoe JA , et al.   Gabapentin for hot flashes in 420 women with breast cancer: A randomized double-blind placebo-controlled trial . Lancet . 2005;366(9488):818–824
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (96 KB)
    • CrossRef
51. Loprinzi CL , Levitt R , Barton D , et al.   Phase III comparison of depomedroxyprogesterone acetate to venlafaxine for managing hot flashes: North Central Cancer Treatment Group Trial N99C7 . J Clin Oncol . 2006;24(9):1409–1414
    • View In Article
    • CrossRef
52. Loprinzi CL , Kugler JW , Barton DL , et al.   Phase III trial of gabapentin alone or in conjunction with an antidepressant in the management of hot flashes in women who have inadequate control with an antidepressant alone: NCCTG N03C5 . J Clin Oncol . 2007;25(3):308–312
    • View In Article
    • CrossRef
53. Newton KM , Buist DS , Keenan NL , et al.   Use of alternative therapies for menopause symptoms: results of a population-based survey . Obstet Gynecol . 2002;100:18
    • View In Article
    • MEDLINE
    • CrossRef
54. Keenan NL , Mark S , Fugh-Berman A , et al.   Severity of menopausal symptoms and use of both conventional and complementary/alternative therapies . Menopause . 2003;10:507
    • View In Article
    • MEDLINE
    • CrossRef
55. Barton DL , Loprinzi CL , Quella SK , et al.   Prospective evaluation of vitamin E for hot flashes in breast cancer survivors . J Clin Oncol . 1998;16(2):495–500
    • View In Article
    • MEDLINE
56. Elkins G , Marcus J , Sterns V , et al.   Pilot evaluation of hypnosis for the treatment of hot flashes in breast cancer survivors . Psychooncology . 2007;16(5):487–492
    • View In Article
    • MEDLINE
    • CrossRef
57. Carpenter JS , Wells N , Lambert B , et al.   A pilot study of magnetic therapy for hot flashes after breast cancer . Cancer Nursing . 2002;25(2):104–109
    • View In Article
    • MEDLINE
    • CrossRef
58. Deng G , Vickers A , Yeung S , et al.   Randomized, controlled trial of acupuncture for the treatment of hot flashes in breast cancer patients . J Clin Oncol . 2007;23(35):5584–5590
    • View In Article
59. Nedstrand E , Wijma K , Wyon Y , et al.   Vasomotor symptoms decrease in women with breast cancer randomized to treatment with applied relaxation or electro-acupuncture: A preliminary study . Climacteric . 2005;8(3):243–250
    • View In Article
    • MEDLINE
    • CrossRef
60. Fisher B , Costantino JP , Wickerham DL , et al.   Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study . J Natl Cancer Inst . 1998;90:1371–1388
    • View In Article
    • MEDLINE
    • CrossRef
61. National Comprehensive Cancer Network  , American Cancer Society  . Breast Cancer Treatment Guidelines for Patients . Atlanta, GA: American Cancer Society; 2006; version VIII
    • View In Article
62. National Comprehensive Cancer Network  . Breast cancer clinical practice guidelines in oncology, version 2, 2006 . Available at: http://www.nccn.org/professionals/physicians_gls/PDF/breast.pdf Accessed September 22, 2009
    • View In Article
63. Baum M , Budzar AU , Cuzick J , et al.   Anastrolzole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early stage breast cancer: First results of the ATAC randomized trial . Lancet . 2002;359:2131–2139
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (150 KB)
    • CrossRef
64. Goss PE , Ingle JN , Martino S , et al.   A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early stage breast cancer . N Engl J Med . 2003;349:1793–1802
    • View In Article
    • CrossRef
65. Howell A , Cuzick J , Baum M , et al.   Results of the ATAC (arimidex, tamoxifen, alone or in combination) trial after completion of 5 years' adjuvant treatment for breast cancer . Lancet . 2005;265:60–62
    • View In Article
    • MEDLINE
66. Thurlimann B . Hormonal treatment of breast cancer: New developments . Oncology . 1998;55:501–507
    • View In Article
    • MEDLINE
    • CrossRef
67. Coombes RC , Hall E , Gibson LJ , et al.   A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer . N Engl J Med . 2004;350:1081–1092
    • View In Article
    • CrossRef
68. Goss PE , Ingle JN , Martino S , et al.   Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: Updated finding from NCIC CTG MA 17 . J Natl Cancer Inst . 2005;97:1262–1271
    • View In Article
    • CrossRef
69. Baum M , Buzdar A , Cuzick J , et al.   Anastrozole alone or in combination with tamoxifen versus tamoxifen alone or for adjuvant treatment of post-menopausal women with early-stage breast cancer: Results of the ATAC (arimidex, tamoxifen alone or in combination) trial efficacy and safety update analyses . Cancer . 2003;98:1802–1810
    • View In Article
    • MEDLINE
    • CrossRef
70. Collaborative Group on Hormonal Factors in Breast Cancer . Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials . Lancet . 2005;365(9472):1687–1717
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (423 KB)
    • CrossRef
71. Bonneterre J , Thrulimann B , Robertson JF , et al.   Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: Results of the tamoxifen or arimidex randomized group efficacy and tolerability study . J Clin Oncol . 2000;18:3748–3757
    • View In Article
    • MEDLINE
72. Perez EA . Safty profiles of tamoxifen and the aromatase inhibitors in adjuvant therapy of hormone-responsive early breast cancer . Ann Oncol . 2007;18(Suppl. 8):26–35
    • View In Article
73. Theriault RL , Biermann JS , Brown E , et al.   NCCN Task Force Report: Bone Health and Cancer Care . J Natl Compr Canc Netw . 2006;S1–S20
    • View In Article
74. Thorne C . Clinical management of arthralgia and bone health in women undergoing adjuvant aromatase inhibitor therapy . Current Opinion in Oncology . 2007;19(Suppl 1):S19–S28
    • View In Article
75. Brown J , Josse R . Clinical practice guidelines for the diagnosis and management of osteoporosis in Canada . CMAJ . 2002;167(Suppl 10):S1–S34
    • View In Article
    • MEDLINE
76. Raisz LG . Clinical practice: Screening for osteoporosis . N Engl J Med . 2005;353:164–171
    • View In Article
    • CrossRef
77. Osowski M . Spinal cord compression: An obstructive oncologic emergency . Medsc Top Adv Pract Nurs . 2002;2(4):1–8
    • View In Article
78. Flaherty AM . Spinal cord compression . In:  Yarbro CH ,  Frogge MH ,  Goodman M ,  Groenwald SL editor. Cancer nursing: Principles and practice . 5th ed.. Sudbury, MA: Jones and Bartlett Publishers; 2000;p. 887–899
    • View In Article
79. Otto SE . Oncology nursing . 5th ed.. St. Louis: Mosby-Yearbook, Inc.; 2007;
    • View In Article
80. Ratliff JK , Cooper PR . Metastatic spine tumors . South Med J . 2004;97(3):246–253
    • View In Article
    • MEDLINE
    • CrossRef
81. Gebaur GP , Farjoodi P , Sciubba DM , et al.   Magnetic resonance imaging of spine tumors: Classification, differential diagnosis, and spectrum of disease . J Bone Joint Surg . 2008;90:146–162
    • View In Article
82. Lin N , Winer EP . Brain metastases: The HER2 paradigm . Clin Cancer Res . 2007;13(6):1648–1655
    • View In Article
    • MEDLINE
    • CrossRef
83. Gori S , Rimondini S , DeAngelis V , et al.   Central nervous system metastases in HER-2-positive metastatic breast cancer patients treated with trastuzumab: incidence, survival, and risk factors . Oncologist . 2007;12(7):766–773
    • View In Article
    • CrossRef
84. Hicks DG , Short SM , Prescott NL , et al.   Breast cancers with brain metastases are more likely to be estrogen receptor negative, express the basal cytokeratin CK5/6, and overexpress HER2 or EGFR . Am J Surg Pathol . 2006;30(9):1097–1104
    • View In Article
    • MEDLINE
85. Diaz-Guzman E , Budev M . Accuracy of the physical examination evaluating pleural effusion . Cleve Clin J Med . 2008;
    • View In Article
86. Weitzen R , Tichler T , Kauffman B , et al.   Body weight, nutritional factors and physical activity—their influence on prognosis after breast cancer diagnosis . Harefuah . 2006;145(11):820–825
    • View In Article
    • MEDLINE
87. American Cancer Society  . Breast cancer facts and figures . Available at: http://www.cancer.org/downloads/STT/500809web.pdf 2009; Accessed September 9, 2009
    • View In Article
88. Irwin ML , McTiernan A , Baumgartner RN , et al.   Changes in body fat and weight after breast cancer diagnosis: influence of demographic, prognostic, and lifestyle factors . J Clin Oncol . 2005;23(4):774–782
    • View In Article
    • MEDLINE
    • CrossRef
89. McTiernanan A . Obesity and cancer: the risks, science, and potential management strategies . Oncology . 2005;19(7):871–881
    • View In Article
90. Sternfeld B , Weltzien E , Quesenberry CP , et al.   Physical activity and risk of recurrence and mortality in breast cancer survivors: findings from the LACE study . Cancer Epidemiol . 2009;18(1):87–95
    • View In Article
91. Blackburn GL , Wang KA . Dietary fat reduction and breast cancer outcome: results from the Women's Intervention Nutrition Study (WINS) . Am J Clin Nutr . 2007;86(3):s878–s881
    • View In Article
92. Chlebowski RT , Blackburn GL , Thomson CA . Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women's Intervention Nutrition Study . J Natl Cancer Inst . 2006;98(24):1767–1776
    • View In Article
    • CrossRef
93. Balard-Barbash R , Hunsberger S , Alciati MH , et al.   Physical activity, weight control, and breast cancer risk and survival: clinical trial rationale and design considerations . J Natl Cancer Inst . 2009;101(9):630–643
    • View In Article
    • CrossRef
94. Ganz P . Quality of life across the continuum of breast cancer care . The Breast J . 2008;6(5):324–330
    • View In Article
95. Turner J , Kelly B , Swanson C , et al.   Psychosocial impact of newly diagnosed advanced breast cancer . Psychooncology . 2005;14(5):396–407
    • View In Article
    • MEDLINE
    • CrossRef

Back to Article Outline

Uncited references 

12. American Joint Committee on Cancer  . What is cancer staging? . Available at: http://www.cancerstaging.org/mission/whatis.html Accessed September 20, 2009
95. Palesh O , Butler LD , Koopman C , et al.   Stress history and breast cancer recurrence . J Psychosom Res . 2007;63(3):233–239