Use of imaging in surveillance of women with early stage breast cancer

Authors

  • Robin J. Bell,

    Corresponding author
    • Women's Health Program, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia
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  • Max Schwarz,

    1. Department of Medicine, Central Clinical School, Monash University, Victoria, Australia
    2. Bayside Health, Alfred Hospital, Victoria, Australia
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  • Pamela Fradkin,

    1. Women's Health Program, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia
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  • Susan R. Davis

    1. Women's Health Program, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia
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  • R. J. Bell MBBS, PhD, MPH, FAFPHM; M. Schwarz MBBS, FRACP, FACP, FAChPM; P. Fradkin MBBS; S. R. Davis MBBS, PhD, FRACP.

Correspondence

Professor Robin Bell, Women's Health Program, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Level 6, The Alfred Centre, 99 Commercial Road, Melbourne, Vic. 3004, Australia. Email: robin.bell@monash.edu

Abstract

Background

There is no evidence of benefit in terms of survival or quality of life for intensive surveillance of women with early breast cancer (BC) and current guidelines reflect this. We have examined whether Victorian women, nearly 4 years from a diagnosis of localized BC, were being managed according to these guidelines.

Methods

Participants are women in the BUPA Health Foundation Health and Wellbeing after Breast Cancer prospective cohort study. All participants completed an enrolment questionnaire within 12 months of diagnosis and then completed follow-up questionnaires every 12 months thereafter. In the third follow-up questionnaire, completed nearly 4 years from the time of diagnosis, women were asked about imaging tests they had in the previous 12 months.

Results

The analysis was completed on 673 women who were stage 1 at the time of diagnosis and had not reported evidence of recurrence or a new BC since diagnosis. Of the 673, 603 (89.5%) reported having had a mammogram in the previous 12 months and 319 (52.9% of those having a mammogram) reported a breast ultrasound. Seventy-one per cent of women reported no other imaging investigations in the previous 12 months.

Conclusions

Our study shows that, nearly 4 years from diagnosis, Australian practitioners are generally adhering to guidelines about imaging surveillance of BC survivors. Practitioners could use the guidelines for the education of BC survivors about appropriate health surveillance.

Introduction

For women who have been treated for sporadic early stage breast cancer (BC), basic surveillance consisting of history, physical examination and mammography is supported by the American Society for Clinical Oncology.[1] In Australia, similar guidelines have been produced by the National Health and Medical Research Council,[2] even though there is no evidence from randomized trials that routine mammography in women with a personal history of BC improves survival from either new ipsilateral or contralateral disease.[3]

Most BC recurrences are detected because they become symptomatic, and evidence of benefit in terms of survival or quality of life for intensive surveillance (including a range of imaging modalities) compared with surveillance where investigations are prompted by clinical indications is lacking.[4] Chest X-rays (CXRs) are not recommended for detecting asymptomatic recurrence because of low sensitivity.[5] Both chest and abdomino-pelvic computerized axial tomography (CAT) examinations are associated with false positive results in women with BC.[6, 7] Bone metastases are usually diagnosed because they present symptomatically, even among women having regular bone scans.[8] Although both magnetic resonance imaging (MRI) and positron emission tomography (PET) are sensitive for the detection of BC, neither is recommended in the routine care of women with a personal history of BC.[9, 10]

Given the current recommendations, our aim was to examine whether women with localized BC at diagnosis and currently nearly 4 years from diagnosis, and free of recurrence or new BC, were being managed according to these guidelines or whether there was evidence of the use of imaging modalities for ‘surveillance’ of women with a history of early BC outside of management guidelines.

Methods

This study was carried out within the BUPA Health Foundation Health and Wellbeing after Breast Cancer Study which is a large prospective cohort study in Australia of women diagnosed between June 2004 and December 2006 with their first episode of invasive BC. The participants were recruited by invitation through the state-based Victorian Cancer Registry.[11] As it is a statutory requirement for organizations involved in the diagnosis of cancer to notify all new cancer diagnoses to the Registry and as there was a low rate of refusal of the invitation to participate in the study, women in the study are representative of all women diagnosed with invasive BC in the state in terms of age, tumour size and location of residence. The details of the individual patient pathology were provided to our study by the Victorian Cancer Registry. Approval for our study has been given by both the Human Research Ethics Committee of the Cancer Council of Victoria as well as the Standing Committee on Ethics in Research Involving Humans of Monash University, and written consent was provided by all participants.

We aimed for all participants to complete the enrolment questionnaire (EQ) within 1 year of diagnosis and the average time between diagnosis, and completion of the EQ was 41 weeks (with 90% of EQs completed between 8 and 58 weeks from diagnosis).[12] The EQ included questions about demographic details, past medical history, details of surgery and other treatments, and questions about the woman's understanding of her cancer. Participants completed follow-up questionnaires (FQs) every year following completion of the EQ (FQ1, FQ2, FQ3). FQs included questions about recurrent disease or the development of a new primary BC, about further treatments, other chronic diseases, as well as validated questionnaires to assess menopausal symptoms and well-being.

The data analysed in this manuscript are from the third follow-up questionnaire (FQ3), which was completed on average 3.8 years from diagnosis (95% were completed between 3.0 and 4.3 years from diagnosis). The data relate to questions about specific follow-up investigations within the previous 12 months including mammography, breast ultrasound (US), CXR, whole body nuclear bone scan (NBS) (as distinct from a dual energy X-ray absorptiometry scan for bone density), CAT scan, MRI scan and PET scan.

For the purposes of this analysis, any participant who reported the presence of active BC (either recurrence or a new primary BC) in any of the FQs up to and including FQ3 was excluded from this analysis as the investigation of that active disease may have involved a range of imaging modalities.

As the guidelines about surveillance relate to women with ‘localised BC’, this analysis is also limited to women with stage 1 disease (tumour diameter of ≤20 mm) with no evidence of tumour cells in the lymph nodes or other parts of the body).[13] Disease which is classified as beyond stage 1 can be so classified because the tumour is >20 mm in diameter or because BC cells have been found in the lymph nodes or in other parts of the body. As there is no question that stage 1 tumours are small and localized to the breast, this analysis was limited to women with stage 1 disease at diagnosis so there was no question that the current guidelines would apply to these women.

The tests the women reported were classified as being ordered in relation to their BC, to another condition or there was no obvious indication for the test or tests. In FQ3, the women were asked whether they had been investigated for a possible recurrence or new BC since completion of the previous questionnaire (and if so, whether on the basis of the test results there was any evidence of recurrence or a new BC). They were asked if they had surgery related to their BC since their previous questionnaire (as the need for surgery such as a reconstruction could be the basis for imaging). They were also asked whether they had been hospitalized since the previous questionnaire (and if so was it due to their BC or another condition; if due to another condition, what was that condition) and whether they had experienced a list of specific conditions including a venous thrombosis or pulmonary embolus, fracture, another cancer or other serious medical conditions. We also asked them if they were participating in a trial as this may have prompted the use of imaging modalities, in which case we classified any tests they had as related to their BC.

As the use of aromatase inhibitors (AIs) is associated with musculoskeletal pain and could prompt the use of NBS, we have indicated numbers of women who reported using an AI among those women who reported having tests other than mammography or breast US.

The results are reported as frequencies and percentages. There was no formal statistical testing performed in relation to the distribution of women on AIs and use of NBS in the groups reporting tests other than mammography and breast US.

Results

Of the 1683 women with a first diagnosis of invasive BC who completed the EQ, 1444 remained in the study by FQ3 (see Fig. 1). Two hundred and thirty-nine women had been lost to the study by this stage because: they had died while remaining a part of the study (64); they had actively withdrawn from the study (contacted our group to tell us they no longer wanted to remain in the study after which they may also have subsequently died) (54); they had passively withdrawn from the study (did not return the next questionnaire despite being reminded to do so by both mail and telephone and then may also have subsequently died) (115); or they were lost to follow-up (6).

Figure 1.

Numbers of women completing the enrolment questionnaire and each of the first three follow-up questionnaires in the BUPA Health Foundation Health and Wellbeing after Breast Cancer Study. %s are of the 1683 women who completed the EQ. EQ, enrolment questionnaire; FQ, follow-up questionnaire.

Of the 1444 women who completed FQ3, 1358 had not reported any active disease (either recurrence or new BC) in any FQ up to and including FQ3 (86 women who remained in the study at FQ3 had reported and been treated for active disease by this time). Of the 1358 women free of active disease by FQ3, 673 were stage 1 at the time of diagnosis and so are included in this analysis.

The characteristics of the complete sample of women recruited to this study have been published elsewhere,[11] however the sample of women in this analysis represent women alive and free of evidence of active disease nearly four years from the time of diagnosis. The mean age of this sample at diagnosis was 58.0 (95% CI 40.0 to 75.2) years and 87% were either oestrogen or progesterone receptor positive, or both.

Mammography and breast US as reported in FQ3

Of the 673 women, 603 (89.5%) reported having had a mammogram in the previous 12 months, 325 reported a breast US in the previous 12 months (48.3%) and 319 (47.4% of the total and 52.9% of those having a mammogram) reported both examinations (Fig. 2). The mean age of the women who had a breast US was 55.8 (SD 10.4) years was significantly lower than the mean age of women who did not have a breast US 60.1 (SD 10.6) years (mean difference 4.3 (95% CI 2.7 to 5.9 years)). Only 64 (9.5%) women had not had either one or other of these examinations in the previous 12 months. Of these 64, 18 had a history of bilateral mastectomy.

Figure 2.

Numbers and proportions of women reporting in the third follow-up questionnaire that they had a mammogram (M), breast ultrasound (US), both or neither in the previous 12 months.

Other imaging modalities (CXR, NBS, CAT, MRI, PET) as reported in FQ3

Of the 673 women, 480 (71%) reported none of these investigations in the previous 12 months. Of the remaining 193 women, 129 (19.2% of the 673) had only one of the investigations (Table 1). The most commonly reported single investigation was a CXR, followed by NBS, CAT scan, MRI and then PET scan. Overall, two thirds of women having a single investigation did not report an indication for the test and this was true for each individual test except for a PET scan (where only five were performed). There was not an over-representation of women on an AI in the group reporting an NBS compared with women reporting one of the other investigations.

Table 1. Numbers of women reporting having only one of CXR, NBS, CAT, MRI or PET in the previous 12 months showing whether the test was performed for their BC, other morbidity or there was no apparent indication for the test
 CXRNBSCATMRIPETTotal (%)
  1. BC, breast cancer; CAT, computerized axial tomography; CXR, chest X-ray; MRI, magnetic resonance imaging; NBS, nuclear bone scan; PET, positron emission tomography. (AI) 39 women taking an aromatase inhibitor as reported in the third follow-up questionnaire.
BC related20

2

(AI, n = 1)

4

(AI, n = 3)

0

8

(6.2)

Other morbidity

19

(AI, n = 2)

7

(AI, n = 3)

61

3

(AI, n = 1)

36

(27.9)

No apparent indication (%)

37

(AI, n = 15)

(63.8)

22

(AI, n = 7)

(75.9)

13

(AI, n = 2)

(61.9)

11

(AI, n = 5)

(68.8)

2

(40.0)

85

(65.9)

Total (%)

58

(44.9)

29

(22.5)

21

(16.3)

16

(12.4)

5

(3.9)

129

Forty-six women reported having two of the investigations (Table 2). The most commonly performed combination of tests was a CXR/NBS followed by a combination of CAT/MRI and CXR/CAT. Overall, just over half of the women having two tests had an obvious indication for the tests, although this proportion varied widely depending on the combination of the tests performed.

Table 2. Numbers of women having a combination of two of the following tests: CXR, NBS, CAT, MRI or PET, in the previous 12 months including whether the tests were performed for their BC, other morbidity or there was no apparent indication for the tests
 CXR and NBSCAT and MRICXR and MRIMRI and PETCXR and CATNBS and CATCAT and PETNBS and MRITotal (%)
  1. BC, breast cancer; CAT, computerized axial tomography; CXR, chest X-ray; MRI, magnetic resonance imaging; NBS, nuclear bone scan; PET, positron emission tomography. (AI) 11 women taking an aromatase inhibitor as reported in the third follow-up questionnaire.
BC related1

1

(AI, n = 1)

110001

5

(10.9)

Other morbidity

3

(AI, n = 1)

5

(AI, n = 1)

20

7

(AI, n = 2)

110

19

(41.3)

No apparent indication

11

(AI, n = 2)

(73.3%)

3

(AI, n = 1)

(33.3%)

0

0%

0

0%

2

(AI, n = 2)

(22.2%)

5

(AI, n = 1)

(83.3%)

1

(50%)

0

0%

22

(47.8)

Total (%)

15

(32.6)

9

(19.6)

3

(6.5)

1

(2.2)

9

(19.6)

6

(13.0)

2

(4.3)

1

(2.2)

46

Sixteen women reported having three of the investigations (Table 3). The most common combination was CXR/CAT/MRI. Two thirds of the women having three tests had an obvious indication for having the tests.

Table 3. Numbers of women reporting having a combination of three of the following tests: CXR, NBS, CAT, MRI or PET, in the previous 12 months, including whether the tests were performed for their BC, other morbidity or there was no apparent indication for the tests
 CXR, NBS, CATCXR, CAT, MRICXR, NBS, MRINBS, CAT, MRITotal (%)
  1. aWomen under 50 years of age at diagnosis. BC, breast cancer; CAT, computerized axial tomography; CXR, chest X-ray; MRI magnetic resonance imaging; NBS, nuclear bone scan. (AI) 6 women taking an aromatase inhibitor as reported in the third follow-up questionnaire.
BC related 1

2

(AI, n = 1)

 

3

(18.8)

Other morbidity2

5

(AI, n = 3)

1a 

8

(50.0)

No apparent indication

3a

(AI, n = 1)

(60.0%)

1a

(14.3%)

0

0%

1

(AI, n = 1)

(100%)

5

(31.2)

Total (%)

5

(31.3)

7

(43.7)

3

(18.7)

1

(6.3)

16

Two women reported having four of the investigations (one had CXR, NBS, CAT and MRI, and the other had NBS, CAT, MRI and PET) and both of them had been investigated for other serious health conditions.

There was no obvious association between the use of an AI at FQ3 and the reporting of an NBS in women having more than one investigation.

Discussion

Our study shows that in relation to mammography, nearly 4 years from diagnosis, Australian practitioners are adhering to guidelines about imaging surveillance of BC survivors. Most women are having annual mammograms; however, more than half of women who had a mammogram also reported having a breast US. The majority of women (71%) did not have any other imaging tests apart from these.

Breast US is not listed in either the ‘recommended’ or the ‘not recommended’ list of investigations for routine surveillance for BC.[1] In our sample, very few women had a breast US without a mammogram and so breast US is essentially being used as supplemental to mammography where clinically indicated. The lower mean age of women reporting breast US is consistent with the use of mammography in younger women who are more likely to have denser breast tissue. Although breast US is generally considered a safe procedure and has been shown to increase the diagnostic yield in a high-risk population, it will also increase substantially the number of women having a biopsy.[14] Even though the sensitivity is improved by the addition of US, despite the extra cancers diagnosed, the extra false positive results result in a reduced positive predictive value of the combination of tests.

Where women did have one or more of tests other than mammography or breast US, the more tests a woman had, the more likely it was that there was a specific reason identified for the tests being ordered, either in relation to her BC or to another medical condition. The use of AIs is associated with musculoskeletal pain in up to 40% of users[15] and could prompt the use of an NBS to exclude bony metastases; however, we found no association between the use of an AI and the use of a NBS either alone or in combination with other tests. The frequency of use of isolated CXRs and NBS suggests that these tests may be being used for some informal ‘surveillance’ by some practitioners, although it is also possible that some women failed to recall indications for a CXR such as a chest infection.

The strengths of our study include that our cohort of women with BC was recruited through the state cancer registry and we have a high rate of retention in our study. This means that our findings can be generalised to all Victorian women with their first episode of invasive BC who remain free of active disease. An additional strength of our study is that the data were collected on average nearly 4 years from diagnosis and so provide an indication of adherence to guidelines well beyond the initial period of acute BC treatment. ‘A recent survey of surgeons and radiologists in the UK found that the most frequently reported time at which women were discharged from surveillance mammography was 10 years, however when initiation, frequency and cessation of mammography were all considered there were over 50 different regimens of surveillance mammography followed’.[16]

A potential weakness of our study is that there may have been indications for the use of the imaging modalities which were not reported by women in FQ3. We tried to minimize this issue by giving the women multiple opportunities within FQ3 to record if the investigation was for reasons related to their BC, investigation of a range of other specified medical conditions as well as conditions not specifically listed. Ideally, one would review medical records to establish the indications for the tests performed; however, as this is a community-based study with participants living throughout the state of Victoria, reviewing all the medical records was not feasible.

The national expenditure on cancer care in the United States in 2006 was $104 billion, with the largest single expenditure being on BC.[17] Costs are increasing because the costs of new treatments are increasing and the proportion of people receiving treatment is also increasing.[18] Another contributor to cost is the surveillance of the health of people living with a cancer diagnosis. The marginal cost of choosing an intensive rather than a minimal surveillance regimen for women with stage I or II BC in the United States was estimated to be $1 billion in the year 2000.[19] Publication of formal guidelines has been shown to be followed by reduced costs of surveillance.[20] Moving away from scheduled to targeted investigation may not only reduce costs but also reduce patient anxiety.[21]

Our data would suggest that in general, Australian health-care providers are practising in line with guidelines. The use of breast US as an ancillary investigation to mammography in this setting is understandable; however, given the observed prevalence of the combined use of mammography and breast US in this group, practitioners need to be aware of the impact of introducing breast US to standard mammography on the false positive rate. Practitioners could use the guidelines for the individual education of BC survivors about the use of imaging in their health surveillance. BC advocacy groups could also play a role in this educative process.

Acknowledgements

The authors wish to thank the study participants and the members of our Study Advisory Group: Dr Jacquie Chirgwin, A/Professor John Collins, Professor Graham Giles, Mr Peter Gregory, Mr Stewart Hart, Miss Suzanne Neil and Mrs Avis McPhee. The authors also wish to thank members of the research team of the Health and Wellbeing after Breast Cancer study, without whose hard work this large cohort study would not be possible (Penny Robinson, Maria La China, Dr Mary Panjari and Jo Bradbury). Finally, we thank Ms Helen Farrugia, Director of Information Systems, and Professor Graham Giles, Director, of the Victorian Cancer Registry, for their ongoing support of this study.

Funding sources

This work was supported by the BUPA Health Foundation (previously the Medical Benefits Fund of Australia Limited Foundation) (to SRD and RJB), the National Health and Medical Research Council of Australia (Grants no. 219279 to SRD and RJB, 490938 to SRD), Novartis Oncology Australia (SRD), the L.E.W. Carty Trust, the Jack and Robert Smorgon Families Foundation, Connie and Craig Kimberley and Roy Morgan Research (all to SRD and RJB). This Research Project was also supported by the Victorian Government through a Victorian Cancer Agency Public Health Research Fellowship (to RJB).

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