Health Management of Breast Cancer Survivors
============================================

* Min Li
* Juan Chen
* Zhendong Chen

## Abstract

Breast cancer is defined as a chronic disease. Increasing amounts of attention have been paid to the health management of breast cancer survivors. An important issue is how to find the most appropriate method of follow-up in order to detect long-term complications of treatment, local recurrence and distant metastasis and to administer appropriate treatment to the survivors with recurrence in a timely fashion. Different oncology organizations have published guidelines for following up breast cancer survivors. However, there are few articles on this issue in China. Using the published follow-up guidelines, we analyzed their main limitations and discussed the content, follow-up interval and economic benefits of following up breast cancer survivors in an effort to provide suggestions to physicians. Based on a large number of clinical trials, we discussed the role of physical examination, mammography, liver echograph, chest radiography, bone scan and so on. We evaluated the effects of the above factors on detection of distant disease, survival time, improvement in quality of life and time to diagnosis of recurrence. The results of follow-up carried out by oncologists and primary health care physicians were compared. We also analyzed the correlation factors for the cost of such follow-up. It appears that follow-up for breast cancer survivors can be carried out effectively by trained primary health care physicians. If anything unusual arises, the patients should be transferred to specialists.

KEY WORDS:
*   breast cancer survivor
*   health management

## Introduction

At present, due to the advanced medical technology, the 5-year survival rate of the patients with breast cancer has reached up to 72% globally[1]. With the increasing number of the breast cancer survivors, more and more attention has been driven to the issue of the health management of these survivors. An important issue is how to find the most appropriate way of follow-up in order to detect the long-term complications of treatment, local recurrence and distant metastasis and give survivors treatment timely. The main content of this article is to discuss this issue.

## Follow-up Guidelines of Different Cancer Organizations

### International Union against Cancer (UICC)

History taking and physical examination every 3-4 months for the first 2 years are recommended[2], then every 6 months for the next 3 years and then annually. A yearly mammographic evaluation should be performed to screen second primary breast cancer. Symptomatic patients should have comprehensive and relevant examinations to identify complications and to exclude recurrence or metastasis. Assess the pre-menopausal women’s risk of osteoporosis. Because of conventional ultrasound and endometrial biopsy showing a high rate of false positive, they are not routinely recommended for asymptomatic women taking tamoxifen unless vaginal bleeding.

### European Society for Medical Oncology (ESMO)

For the survivors of the primary breast cancer[3], history taking, eliciting symptoms and physical examination are recommended as follows, every 3-6 months for the first 3 years, then every 6-12 months for the following 3 years, and then annually, with attention being paid to long-term side effects, e.g. osteoporosis. Ipsilateral (after breast-conserving surgery) and contralateral mammography every 1-2 years is recommended. For the asymptomatic patients, the examinations of blood counts, chemistry, chest X-ray, bone scan, liver ultrasound, CT scans of chest and abdomen, and any tumor markers such as CA153 or CEA are not routinely recommended.

For the patients with local recurrence or metastasis of breast cancer[4], the regular follow-up after the treatment against the local-regional recurrence may be carried out at the same frequency as those for primary breast cancer patients. Patients must be seen frequently and receive the best way for symptom control so as to promote quality of life.

### National Comprehensive Cancer Network (NCCN)

For the patients with lobular carcinoma in situ[5], the interval history taking and physical examination every 6-12 months and mammogram every 12 months, unless post-bilateral mastectomy, should be done. For the patients with ductal carcinoma in situ, there some recommendations as follows, the interval history taking and physical examination every 6-12 months for the first 5 years, and then annually, and mammogram every 12 months. For the patients with invasive breast cancer, the follow-up examinations include the interval history taking and physical examination every 4-6 months for the first 5 years and then every 12 months, and the mammogram every 12 months (6-12 months post-radiation therapy if breast conserved). If the women take tamoxifen, the gynecologic assessments need to be done every 12 months if uterus is remained. If the women have aromatase inhibitor or experience ovarian failure secondary to the treatment against breast cancer, they need monitoring of bone density, at the same time, the compliance of the patients to adjuvant endocrine therapy should be assessed and persistent treatment is encouraged.

### World Health Organization (WHO)

History taking and physical examination are recommended every 3-6 months for the first 3 years[6], every 6-12 months for the next 2 years and then annually, with attention paid to long-term side effects, such as, osteoporosis. Ipsilateral (after breast-conserving surgery) or contralateral mammography need to be done every 1-2 years. Blood counts, chemistry, chest X-rays, bone scans, liver ultrasound, CT scans on chest and abdomen, and monitoring of tumor markers such as CA153 and CEA are not routinely recommended for asymptomatic patients. Because of the risk of tamoxifen-associated endometrial cancer, a yearly pelvic examination coupled with evaluation of vaginal spotting is essential. The performance of endometrial biopsy or ultrasound is not recommended.

### American Society of Clinical Oncology (ASCO)

All patients should have a careful history taking and physical examination performed by a physician experienced in the surveillance of cancer patients and in breast examination[7]. Examinations should be performed every 3-6 months for the first 3 years, every 6-12 months for the following 4 and 5 years, and annually thereafter. For those who have undergone breast-conserving surgery, a post-treatment mammogram should be obtained 1 year after the initial mammogram and at least 6 months after completion of radiation therapy. Thereafter, unless otherwise indicated, a yearly mammographic evaluation should be performed. The use of CBCs, chemistry panels, bone scans, chest radiographs, liver ultrasound, computed tomography scans, 18F-fluorodeoxyglucose positron emission tomography scanning, magnetic resonance imaging, or tumor markers (carcinoembryonic antigen, CA153, and CA27.29) is not recommended for routine follow-up of breast cancer patients in an otherwise asymptomatic patient with no specific findings on clinical examination.

The follow-up guidelines of different oncology organizations have recommended the performances of history taking, physical examination and mammogram as basic contents of the follow-up, and meanwhile suggested to assess the risk of osteoporosis for the patients who take aromatase inhibitors. NCCN has set up the follow-up guidelines depending on different pathological types. But different agencies who carry out the follow-up work have different views on the interval of monitoring endometrial cancer. Some other issues have still existed, such as, which follow-up could detect the long-term complications of treatment, local recurrence and distant metastasis and give survivors treatment timely at a minimum cost. Whether or not, is sufficient to just carry out the projects recommended by guidelines and why not to recommend some common contents in clinical practice. We will discuss these issues in the following part.

## Contents and Problems

### History taking, Physical Examination and Patient Education Regarding Symptoms of Recurrence

Above issues are the basic examinations. Physicians should inform the patients about the symptoms of recurrence including new lumps, bone pain, chest pain, dyspnea, abdominal pain or persistent headaches. Distribute the booklets to patients, in which relevant knowledge of recurrent symptoms is printed, or suggest patients to buy relevant books or go to the Internet. Tell patients to see doctor immediately if these symptoms occur. In addition, more than half of the patients who have breast cancer recurrences are a symptomatic and their recurrence are found during the scheduled follow-up visits. A recent meta-analysis[8] of 12 studies involving 5045 patients found that 40% of the patients with loco-regional recurrences were found during the routine clinical visits or routine testing, whereas the other patients (approximately 60%) who developed symptomatic recurrences visited the doctor at the time when they realized the symptoms.

### Mammography

A study enrolled 1,846 patients with breast cancer of stage I and stage II whose age was at least 65 years old[9]. They found each additional surveillance mammogram was associated with a 0.69 fold decrease in the breast cancer mortality (95% CI, 0.52 to 0.92). The favourable association was strongest among women with Stage I, those who received mastectomy, and those in the oldest age group. Lash et al.[10] conducted a case-control analysis nested in a cohort of 865 breast cancer patients in Stage I or IIdiagnosed from 1996-1999. They found that the mortality rate declined with an increasing number of mammograms (*P* = 0.007). The age- and therapy-adjusted odds ratio associating receipt of an additional mammogram, compared with receipt of no mammogram, equaled 0.77 (95% CI 0.53-1.1). There is no dispute among the researchers that mammography is a regular program of the follow-up. But its best interval hasn’t been confirmed.

### Transvaginal Ultrasound (TVUS)

As the most common endocrine drug, tamoxifen used to treat breast cancer patients also increases the occurrence of endometrial cancer risk. How are the tamoxifen-treated patients follow up? Could the examination, of endometrial thickness by TVUS, determine the endometrial cancer timely? Gerber et al.[11] conducted a study on this issue. Endometrium of 247 tamoxifen-treated (20-30 mg/d for ≥ 2 years) women were prospectively monitored in their follow-ups by mense of TVUS every 6 months for up to 5 years. Patients with homogeneous endometrium of more than 10-mm thickness were then checked every 3 months. Fifty-two asymptomatic patients with thickened or morphologically suspect endometrium underwent hysteroscopy and dilatation and curettage, resulting in 4 cases of uterine perforations. In histopathological examination, atrophy was found in 38 patients (73.1%), polyps in 9 hyperplasia in 4 and endometrial cancer in 1 case. In tamoxifen-treated patients, TVUS offered a high false-positive rate, even with a cutoff value of 10mm for endometrial thickness and repeated TVUS scans. Because of the increased iatrogenic morbidity and the low rate of asymptomatic endometrial carcinoma, endometrial screening used TVUS in tamoxifen-treated patients couldn’t make a definite diagnosis.

### Chest radiograph, Bone Scan, CT Scan and Laboratory Test

Joseph et al.[12] identified 120 patients with recurrent disease from a prospective database of 1,898 breast cancer patients. The patients with recurrent disease were divided into regular follow-up (history, physical examination and mammogram) or intensive follow-up (frequent laboratory tests, chest radiographs, bone scans, CT scans) group. The result of this study showed that there was no survival benefit to routine intensive follow-up regimens in detecting recurrent breast cancer. At the same time, a follow-up study of 1,243 breast cancer patients also confirmed the results of the previous study[13].

### Breast Magnetic Resonance Imagine (MRI)

A cohort study[14] of 529 women at high risk for breast caner based on family history found that MRI showed a higher sensitivity than mammography (91% *vs*. 33%) in detecting breast cancer, whereas specificity shown by both tools was similar (97.2% *vs*. 96%). Although MRI used in breast screening seems to be more sensitive than conventional imagine dose in detecting breast caner in high-risk women, there is no evidence that breast MRI improves outcomes when used as a breast cancer surveillance tool during routine follow-up in asymptomatic breast caner patients. A retrospective study[15] of 476 patients undergoing margin-negative lumpectomy and adjuvant radiation therapy for infiltrating breast carcinoma followed for a median of 5.4 years found that ipsilateral breast cancer recurrence was developed in eight patients (1.7%) with a mean diameter of 1.6 cm. All of the 8 women are alive and free of metastases. Contra lateral breast cancer was developed in 11 patients (2.3%) with a mean diameter of 1.5 cm. Ten of the 11 women are alive and free of disease. In the contemporary patient population, the risk of local recurrence after lumpectomy and radiation therapy is very low. If screening MRI had been a part of annual follow-up, a total 1,570 MRIs would have been performed during the 4.5 years. Given the small tumor size at detection and the excellent survival of those whose cancer recurred, annual screening MRI would have significant cost and would have been unlikely to improve overall survival.

### 18F-Fluorodeoxyglucose Positron Emission Tomography Scanning

We reviewed several recent studies that pertain to surveillance issues in breast cancer patients. Available data on FDG-PET scanning in breast cancer surveillance come from retrospective cohort studies. There are no prospective randomized trial data. One cohort study prospective randomized trial data. One cohort study of 61[16] patients compared FDG-PET scanning with conventional imaging for detecting residual or recurrent breast cancer. Sensitivity of FDG-PET was slightly improved compared with conventional imaging (93% *vs*. 79%; *P* < 0.5), but there was no difference in positive predictive value or specificity between the two tools. The negative predictive value of FDG-PET was also improved compared with conventional imaging (84% *vs*. 59%; *P* < 0.5), but the impact of these results on survival, quality of life, and cost was not evaluated. Another study[17] evaluated the efficacy of whole body FDG-PET scanning in 60 women with clinical or radiographic suspicion of recurrent breast cancer. Forty women were histologically proven relapsed disease. PET scanning was sensitive and specific for loco-regional and distant relapse. Patients enrolled into this non-randomized study already evidence of recurrence (clinically or by conventional radiologic testing); thus, no conclusions can be drawn with regard to survival or other benefits from FDG-PET scanning.

### Tumor Markers of Breast Cancer

The use of tumor markers is not recommended for routine surveillance of breast cancer patients after initial treatment. A study recruited 109 patients with distant metastases[18]: Thirty-six (53%) received salvage treatment at the time of significant increase in one or more components of CEA-TPA-CA153 tumor marker panel and negative instrumental examinations (tumor marker guided treatment) and 32 (47%) were treated only after radiological confirmation of metastases (conventional treatment). The prognostic factors of the 2 groups did not show any statistically significant difference. The time spent for one or more tumor marker increased to clear clinical and/or radiological signs of distant metastases (lead time) was significantly prolonged in the 36 patients with tumor marker guided treatment as well as the survival curves. The above findings demonstrated an increasing need for trials of clinical randomized and controlled in large scale of the samples, so as to assess tumor markers’ influence on improving overall survival or detecting recurrence.

### Who Take the Responsibility For the follow-up

Most practice follow-up guidelines recommend regular history, physical examination, and mammography as the appropriate breast cancer follow-up 1 year after diagnosis. So primary care physician (PCP) can take the responsibility for the follow-up. At the same time PCP and patients should be informed of the appropriate follow-up and management strategies, when the abnormal signs are found by the patients and PCP, the patients should be referred to see the specialist. One randomized[19] clinical trial was designed specifically to evaluate whether PCPs, instead of cancer specialist, can safely provide breast cancer surveillance. This trial involved 296 women randomly assigned to continued specialist follow-up (control group) or to their own general practitioner for follow-up. The median time spent for the confirmation of recurrence was 21 days in the hospital group (range 1-376 days) and 22 days in the general practitioner group (range 4-64 days) respectively. General practice follow up of women with breast cancer in remission is not associated with the increased time of diagnosis, increased anxiety, or decreased health related quality of life. This study has been replicated in Canada involving 968 early-stage breast cancer patients who had completed adjuvant treatment and were observed for a median of 4.5 years from diagnosis[20]. Patients may have continued receiving adjuvant hormonal therapy. Patients were randomly allocated to the cancer center for follow-up or to their own family physician for follow-up. No statistically significant differences were detected between the groups on health-related quality of life or recurrence-related serious clinical events. So trained primary care physician can take the responsibility for the follow-up of the asymptomatic patients.

In order to reduce the costs of the patients and burden of the physicians, there are some studies evaluating the telephone follow-up, but not comparing with the out-patient follow-up. At present, the main form of follow-up is for the out-patients because physician can contact and examine the patients, and judge any problems timely basing on the patients’ symptoms. These advantages could not be reflected in other form of follow-up.

### Economic Outcomes

Hensley et al.[21] investigated breast cancer survivors in the United States to know the contents, frequency and cost of follow-up every year for every patient. The following percentages of survivors reported having had, for breast cancer follow-up, at least once in the past year: breast examination 92%, mammogram 88%, chest radiograph 59%, tumor marker studies 37%, bone scan 18%. Median annual cost of follow-up per survivor was US 630 dollars (ranging from US 0-10,817 dollars). The higher costs were associated with the medical oncology follow-up, lower income, and younger age. When follow-up care involved an oncologist, resources were more likely to be used appropriately, or over-used. At present, many patients and doctors have a prejudice that increasing frequency, contents of follow-up can detect recurrence earlier and improve prognosis. This prejudice results in excessive use of medical resources and increasing social burden. Some patients may have difficulties in finding jobs because employers may concern the survivors’ competency and the cost of the treatment for rehabilitation that can increase their employment costs. Due to the incorrect understanding of breast cancer and the sense of inferiority caused by the changes in their physical, many asymptomatic patients give up the right of access to social work. Therefore, to reduce the financial burden, we should strengthen the education to the whole society, families of the patients and survivors, and reduce the unnecessary test, and encourage the survivors to participate in the social work.

## Conclusion

There are different views of contents, interval and duration of follow-up work. Which follow-up could detect the long-term complications of the treatment, local recurrence and distant disease and give survivors treatment timely at a minimum cost? This issue needs more studies with large samples to be resolved. But the general view is that the follow-up can be carried out by trained primary health care physicians and that careful history taking, physical examination and mammography are performed. But if something is unusual, the patients should be transferred to the specialist to have relevant examinations.

*   Received January 12, 2009.
*   Accepted May 19, 2009.


*   Copyright © 2009 by Tianjin Medical University Cancer Institute & Hospital and Springer

## References

1.  Navarrete Montalvo D, González MN, Montalvo V MT, et al. Patterns of recurrence and survival in breast cancer. Oncol Rep 2008; 20: 531-535.
    
    [PubMed](http://www.cancerbiomed.org/lookup/external-ref?access_num=18695902&link_type=MED&atom=%2Fcbm%2F6%2F3%2F174.atom) 

2.  Pollock RE, Doroshow JH, Khayat D, et al. UICC Manual of Clinical Oncology. USA: John Wiley&Sons Press 2004.
    
    

3.  ESMO Guidelines Working Group. Primary breast cancer: ESMO Clinical Recommendations for treatment and follow-up. Ann Oncol 2008; 19: 7-10.
    
    

4.  ESMO Guidelines Working Group. Locally recurrent or metastatic breast cancer: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Ann Oncol 2008; 19: 11-13.
    
    

5.  Wang G, Wu L, Zheng DY, et al. NCCN Breast Cancer Practice Guidelines. Zhongguo Xunzheng Yixue Zazhi 2005; 5: 247-254.
    
    

6.  World Health Organization. Regional Office for Eastern Meditarranean. Guidelines for the management of breast cancer. Cairo: World Health Organization Press 2006; 22.
    
    

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: 5091-5097.
    
    [Abstract/FREE Full Text](http://www.cancerbiomed.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjEwOiIyNC8zMS81MDkxIjtzOjQ6ImF0b20iO3M6MTc6Ii9jYm0vNi8zLzE3NC5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

8.  Bonnema J, van der Hage J, Kievit J, et al. Effectiveness of routine visits and routine tests in detecting isolated locoregional recurrences after treatment for early-stage invasive breast cancer: A meta-analysis and systematic review. J Clin Oncol 2004; 22: 4010-4018.
    
    [Abstract/FREE Full Text](http://www.cancerbiomed.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjEwOiIyMi8xOS80MDEwIjtzOjQ6ImF0b20iO3M6MTc6Ii9jYm0vNi8zLzE3NC5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

9.  Lash TL, Fox MP, Buist DS, et al. Mammography surveillance and mortality in older breast cancer survivors. J Clin Oncol 2007; 25: 3001-3006.
    
    [Abstract/FREE Full Text](http://www.cancerbiomed.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjEwOiIyNS8yMS8zMDAxIjtzOjQ6ImF0b20iO3M6MTc6Ii9jYm0vNi8zLzE3NC5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

10. Lash TL, Fox MP, Silliman RA. Reduced mortality rate associated with annual mammograms after breast cancer theraphy. Breast J 2006; 12: 2-6.
    
    [CrossRef](http://www.cancerbiomed.org/lookup/external-ref?access_num=10.1111/j.1075-122X.2006.00177.x&link_type=DOI) 
    
    [PubMed](http://www.cancerbiomed.org/lookup/external-ref?access_num=16409580&link_type=MED&atom=%2Fcbm%2F6%2F3%2F174.atom) 

11. Gerber B, Krause A, Muller H, et al. Effects of adjuvant tamoxifen on the endometrium in postmenopausal women with breast cancer: a prospective long-term study using transvaginal ultrasound. J Clin Oncol 2000; 18: 3464-3470.
    
    [Abstract/FREE Full Text](http://www.cancerbiomed.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjEwOiIxOC8yMC8zNDY0IjtzOjQ6ImF0b20iO3M6MTc6Ii9jYm0vNi8zLzE3NC5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

12. Joseph E, Hyacinthe M, Lyman GH, et al. Evaluation of an intensive strategy for follow-up and surveillance of primary breast cancer. Ann Surg Oncol 1998; 5: 522-528.
    
    [CrossRef](http://www.cancerbiomed.org/lookup/external-ref?access_num=10.1007/BF02303645&link_type=DOI) 
    
    [PubMed](http://www.cancerbiomed.org/lookup/external-ref?access_num=9754761&link_type=MED&atom=%2Fcbm%2F6%2F3%2F174.atom) 
    
    [Web of Science](http://www.cancerbiomed.org/lookup/external-ref?access_num=000075863000008&link_type=ISI) 

13. Palli D, Russo A, Saieva C, et al. Intensive vs. Clinical Follow-up after treatment of primary breast cancer: 10-year Update of a randomized trial. JAMA 1999; 281: 1586.
    
    [CrossRef](http://www.cancerbiomed.org/lookup/external-ref?access_num=10.1001/jama.281.17.1586&link_type=DOI) 
    
    [PubMed](http://www.cancerbiomed.org/lookup/external-ref?access_num=10235147&link_type=MED&atom=%2Fcbm%2F6%2F3%2F174.atom) 
    
    [Web of Science](http://www.cancerbiomed.org/lookup/external-ref?access_num=000080025900018&link_type=ISI) 

14. 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.
    
    [Abstract/FREE Full Text](http://www.cancerbiomed.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjEwOiIyMy8zMy84NDY5IjtzOjQ6ImF0b20iO3M6MTc6Ii9jYm0vNi8zLzE3NC5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

15. Gorechlad JW, McCabe EB, Higgins JH, et al. Screening for recurrences in patients treated with breast-conserving surgery: is there a role for MRI? Ann Surg Oncol 2008; 15: 1703-1709.
    
    [CrossRef](http://www.cancerbiomed.org/lookup/external-ref?access_num=10.1245/s10434-008-9832-2&link_type=DOI) 
    
    [PubMed](http://www.cancerbiomed.org/lookup/external-ref?access_num=18266039&link_type=MED&atom=%2Fcbm%2F6%2F3%2F174.atom) 

16. Vranjesevic D, Filmont JE, Meta J, et al. Whole body (18)F-FDG PET and conventional imaging for predicting outcome in previously treated breast cancer patients. J Nucl Med 2002; 43: 325-329.
    
    [Abstract/FREE Full Text](http://www.cancerbiomed.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoiam51bWVkIjtzOjU6InJlc2lkIjtzOjg6IjQzLzMvMzI1IjtzOjQ6ImF0b20iO3M6MTc6Ii9jYm0vNi8zLzE3NC5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

17. Kamel EM, Wyss MT, Fehr MK, et al. [18F]-Fluorodeoxyglucose positron emission tomography in patients with suspected recurrence of breast cancer. J Cancer Res Clin Oncol 2003; 129: 147-153.
    
    [PubMed](http://www.cancerbiomed.org/lookup/external-ref?access_num=12712329&link_type=MED&atom=%2Fcbm%2F6%2F3%2F174.atom) 
    
    [Web of Science](http://www.cancerbiomed.org/lookup/external-ref?access_num=000183106300002&link_type=ISI) 

18. Nicolini A, Carpi A, Michelassi C, et al. “Tumour marker guided” salvage treatment prolongs survival of breast cancer patients: final report of a 7-year study. Biomed Pharmacother 2003; 57: 452-459.
    
    [CrossRef](http://www.cancerbiomed.org/lookup/external-ref?access_num=10.1016/j.biopha.2003.09.004&link_type=DOI) 
    
    [PubMed](http://www.cancerbiomed.org/lookup/external-ref?access_num=14637388&link_type=MED&atom=%2Fcbm%2F6%2F3%2F174.atom) 
    
    [Web of Science](http://www.cancerbiomed.org/lookup/external-ref?access_num=000187020800003&link_type=ISI) 

19. Grunfeld E, Mant D, Yudkin P, et al. Routine follow up of breast cancer in primary care: randomised trial. BMJ 1996; 313: 665-669.
    
    [Abstract/FREE Full Text](http://www.cancerbiomed.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiYm1qIjtzOjU6InJlc2lkIjtzOjEyOiIzMTMvNzA1OC82NjUiO3M6NDoiYXRvbSI7czoxNzoiL2NibS82LzMvMTc0LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

20. 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: 848-855.
    
    [Abstract/FREE Full Text](http://www.cancerbiomed.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjg6IjI0LzYvODQ4IjtzOjQ6ImF0b20iO3M6MTc6Ii9jYm0vNi8zLzE3NC5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

21. Hensley ML, Dowell J, Winer E, et al. Economic outcomes of breast cancer survivorship. CALGB study 79804. Breast Cancer Res Treat 2005; 91: 153-161.
    
    [CrossRef](http://www.cancerbiomed.org/lookup/external-ref?access_num=10.1007/s10549-004-6497-9&link_type=DOI) 
    
    [PubMed](http://www.cancerbiomed.org/lookup/external-ref?access_num=15868443&link_type=MED&atom=%2Fcbm%2F6%2F3%2F174.atom) 
    
    [Web of Science](http://www.cancerbiomed.org/lookup/external-ref?access_num=000228867600007&link_type=ISI)