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Are too many breast cancers missed at assessment?
The Breast (2000) 9, 201–207 © 2000 Harcourt Publishers Ltd doi:10.1054/brst.2000.0184, available online at http://www.idealibrary.com on
ORIGINAL ARTICLE
Are too many breast cancers missed at assessment? J. Liston Leeds Wakefield Breast Screening Service, Seacroft Hospital, Leeds, UK. S U M M A R Y. Interval breast cancers presenting between screening episodes are an inevitable occurrence but their number should to be kept to a minimum. The objectives of this study were to ascertain the proportion of interval cancers developing in women who had been recalled for assessment after their initial screen and to review the assessment process. Interval cancers presenting after false negative assessment accounted for a small proportion (6%) but some cancers may have been diagnosed earlier if image guided FNAC or core biopsy had been included in the assessment process. © 2000 Harcourt Publishers Ltd
INTRODUCTION
to be surprisingly high, although it was not known whether the cancer had been incorrectly assessed or whether the woman had been recalled for a different lesion. This retrospective study was undertaken to ascertain the magnitude of the problem at the Leeds Wakefield Breast Screening Service.
Interval breast cancers, defined as cancers arising less than 36 months after a negative screening mammogram are an expected and unavoidable occurrence within a screening programme, but their numbers need to be kept as low as possible if mortality reductions in the screened population are to be achieved. The aim of NHS Breast Screening Programme as given in ‘Health of the Nation’ (Secretary of State for Health 1992) is to reduce mortality from breast cancer amongst women in the screening age group by 25%. Minimising the number of interval cancers should also reduce the risk of litigation. A survey conducted by Professor Field1 reported that 27% of screening units in the UK had been involved in litigation at some time. Approximately half of the cases were current and most arose due to cancers in whom the diagnosis had been delayed. Unrealistic public expectation fuelled by the press is partly to blame, but society as a whole is becoming increasingly litigious. Published papers have documented the number of interval cancers arising at different time intervals after screening, but there are few published data on the number of women who have attended for further assessment before being reassured that breast cancer has been excluded. The Scottish Breast Screening Programme recently published data2 stating that 16% of women who developed an interval cancer had attended an assessment clinic. The number was thought
METHOD Accurate and timely ascertainment of interval cancer data is acknowledged to be difficult. In the Yorkshire part of the Northern & Yorkshire region we are fortunate to have systematic sharing of information between the Northern & Yorkshire Cancer Registry Information Service (formally the Yorkshire Cancer Registry) and the Quality Assurance Reference Centre for Breast Screening. The Cancer Registry informs an officer from the Quality Assurance Reference Centre of all newly registered cases of breast cancer. The details are manually correlated with data held at each of the four screening units and each case classified as either a screen detected cancer, interval cancer, cancer in a lapsed attender, cancer in a non-attender, or cancer in a woman who has not been invited for screening in accordance with the NHSBSP guidelines on the collection and use of breast cancer data.3 Ascertainment of interval cancer cases developing up to three years after a negative screen is thought to be complete for women screened between January 1991 and March 1995. The Yorkshire breast screening radiologists meet every three months to review and classify interval cancer cases by
Address correspondence to: Dr J Liston MBBS, FRCR, Leeds Wakefield Breast Screening Service, Seacroft Hospital, Leeds LS14 6UH, UK. Tel.: 0113 206 3769; Fax: 0113 206 3796
201
202
The Breast
the method outlined in the NHSBSP Quality Assurance Guidelines for Radiologists.4 All interval cancer cases known to the Leeds Wakefield Breast Screening Service on 21 December 1998 were retrospectively reviewed to ascertain if they had attended an assessment clinic, and if so a detailed analysis was made of the tests performed.
RESULTS Table 1 shows the number of interval cancers and the rate per 10,000 women screened with 95% confidence intervals by screening year cohort for the periods up to 12, 24 and 36 months since the last negative screen. To date, a total of 256 intervals cancers have been identified in the 144,208 women screened between 1991 and 31 March 1998. The number of interval cancers registered within one, two and three years of screening were 66, 95, and 95 respectively, although these numbers will increase with further follow-up. Table 1 also shows the invasive cancer detection rates. Between 1991 and 31 March 1998, 730 breast cancers were screen detected, 585 of which were invasive cancers. Ascertainment of interval cancer data (< 24 months) is thought to be complete for all women screened up until March 1996, with complete three year data for women screened prior to April 1995. The rate of interval cancers presenting within two years of a negative screen is 14.2/10,000 screened and the rate presenting in the third year after a negative screen is 12.0/10,000 screened. Interval cancers developing in women who had been recalled for further assessment after screening accounted for 31 (12%) of the 256 cases. Further analysis found that 7 of the women had been recalled for further assessment of their
contralateral breast, and 8 women because of an apparent abnormality in the same breast in which a cancer subsequently developed, but at a different site. The remaining 16 (6%) women had been recalled for assessment of an abnormality which subsequently grew and presented symptomatically as an interval cancer. This small group of women had undergone false negative assessment and been falsely reassured. Details of the procedures undertaken at the assessment clinic are given in Table 2. The women ranged in age from 49–63 years (mean 56 years) when their initial screen was undertaken. Eight were recalled for assessment of a mass(es), 6 for possible stromal deformity and one for calcification. One woman was recalled as she told the radiographers that she could feel a lump in her breast. Ultrasound was performed in all except the calcification case and one of the cases of stromal deformity. All women were clinically examined – 10 had no palpable abnormality, 5 had a focal area of palpable thickening and one a palpable lump thought to be benign. Assessment included needle biopsy (FNAC or core biopsy) in only 5 women. Table 3 documents the time between screening and development of the interval cancer and gives pathological details. The interval ranged between 4 and 32 months (mean 15 months). All cases except one presented symptomatically with either a palpable lump or distortion. The other was detected on a mammogram taken as part of a family history screen. The cancers were of varied type and ranged in size from 4–38 mm (mean 16 mm). Nine were node negative, 4 were node positive but with less than 4 nodes involved. The node status was unknown in 3 cases including case 7 who presented with clinically advanced carcinoma which was treated with primary chemotherapy.
Table 1 Numbers of interval cancers, rate per 10,000 women screened, and 95% confidence intervals for the periods up to 12, 24 and 36 months since the last negative screen. The invasive cancer detection rate per 10,000 women is also given Screening year
Number of women screened
Invasive cancer detection rate per 10,000
Number of interval cancers Rate per 10,000 women screened (95% CI) 0 – < 12 months 12 – < 24 months – – 7 4.4 11 5.3 14 6.5 14 7.4 7 3.6 4 2.0 8*
1990–91
1364
36
1991–92
15,970
32
1992–93
20,559
38
1993–94
21,635
41
1994–95
18,833
36
1995–96
19,684
39
1996–97
19,948
41
1997–98
26,215
*Ascertainment incomplete.
51
(1.7 to 9.0) (2.7 to 9.6) (3.5 to 10.8) (4.1 to 12.5) (1.4 to 7.3) (0.5 to 5.1)
2 14.6 18 11.2 (6.6 to 17.8) 15 7.3 (4.1 to 12.0) 22 10.2 (6.4 to 15.4) 16 8.5 (4.8 to 13.8) 14 7.1 (3.9 to 11.9) 8*
24 – < 36 months 2 14.6 16 10.0 (5.7 to 16.2) 30 14.6 (9.8 to 20.8) 24 11.1 (7.1 to 16.5) 12 6.4 (3.3 to 11.1) 10* 1*
Are too many breast cancers missed at assessment? 203 Table 2 Case
Tests undertaken at assessment Age when screened
Date of assessment
Mammogram report
Ultrasound report
Clinical examination
FNAC/core biopsy
1 2
61 56
9/91 4/92
– –
50
8/92
Normal
–
4
49
3/93
Thickening
–
5
63
2/93
?Stromal Deformity → composite (RN) Normal (RN)
Cyst Solid masses 3 2 Solid mass ?intramammary lymph node Normal
Normal Normal
3
10 mm Mass (RB) 15 mm + 10 mm masses (RB) 15 mm mass (RS) but unchanged in 2 years
Normal
–
6
56
6/93
14 mm mas (RU)
Thickening (bilateral) Normal
7
61
6/93
Normal
C2 (stereo guided)
8
53
8/93
Solid masses 32
Normal
–
9
59
2/94
–
Normal
–
10
53
3/94
9 mm cyst
Palpable lump (PB)
–
11 12
53 53
5/94 10/94
Solid mass Normal
Thickening Thickening
C2 (u/s guided) –
13
56
2/95
?Stromal deformity (RU) 12 mm masses (RB + RU) but unchanged in 2 years ?Stromal Deformity → composite (RN) Asymmetry + ?Stromal deformity → composite (RB) 10 mm mass (RB) ?Stromal deformity → composite (RN) 10 mm Mass (RB)
Normal
C2 with lymphoid cells (u/s guided)
14 15
50 60
11/95 6/96
Solid mass ?Intramammary lymph node Cysts Area of benign breast change
Normal Thickening
– C3 + C2 (clinical)
16
59
7/96
–
Normal
B2 (stereo guided)
Bilateral masses (RB) Asymmetry + ?Stromal deformity → composite (RB) New calcification (RU)
Cyst with low level echoes Normal
–
RN/RB/RU/RS = Radiologically normal/benign/uncertain/suspicious.
Table 3
Pathology of interval cancers
Case
Interval (Months)
Pathology
Lymph Node Status
1 2 3 4 5 6 7 8* 9* 10 11 12 13 14 15* 16
15 32 11 25 6 16 16 13 14 10 14 12 4 17 12 28
38 mm Primary Breast Sarcoma 20 mm NST (II) + fibroadenoma 14 mm NST (II) 20 mm lobular Ca 12 mm NST (II) 15 mm NST (grade unknown) Rx Primary chemotherapy 15 mm NST (I) + fibroadenoma 4 mm NST/Tubular (II) 7 mm NST (II) 14 mm Intracystic papillary Ca + 2 mm NST (I) 15 mm Tubular Ca 10 mm Mucinous Ca (I) 20 mm NST (III) 18 mm NST (I) 22 mm NST (II)
0/13 0/13 – 0/7 0/14 2/5 – 0/22 0/21 – 1/9 1/6 0/2 0/7 3/9 0/9
*Wire guided.
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Table 4
Comparison of screening/assessment imaging with imaging performed at the time of symptomatic presentation – a retrospective review
Case
Screening/Assessment Imaging
Symptomatic Imaging 50 mm poorly defined mass
11
10 mm mass with unclear margins thought to represent a ‘cyst’ with ultrasound a) 10 mm solid mass with unclear margins b) 15 mm solid mass with unclear margins 15 mm solid mass with irregular margins unchanged over 2 years Possible stromal deformity/normal ultrasound 15 mm ill-defined asymmetry 14 mm mass with unclear margins thought to represent a ‘cyst’ with ultrasound Possible stromal deformity a) 12 mm solid mass with unclear margins b) 12 mm solid mass with well defined margines 10 mm area of asymmetry + possible distortion Asymmetry + possible stromal deformity 9 mm ‘cyst’ imaged with ultrasound 10 mm well-defined solid mass
12
Possible stromal deformity/normal ultrasound
13 14
10 mm well-defined solid mass RT – 10 mm mass with unclear margins thought to represent a ‘cyst’ with ultrasound LT – 8 mm mass with unclear margins thought to represent a ‘cyst’ with ultrasound 30 mm irregular asymmetry + possible distortion Ultrasound imaged benign breast change only Small cluster of new calcification
1 2 3 4 5 6 7 8 9 10
15 16
DISCUSSION The number of interval cancers presenting within the first two years of a negative screen at the Leeds Wakefield Breast Screening Service exceeds the NHSBSP4,5 expected rate of less than 12.0/10,000 screened, but are comparable with other UK and European published data – Nijmegen,6 North West Region,7 East Anglia,8 Yorkshire9 and the recent Scottish data.2 The third year rate is comparable to the Yorkshire and Scottish data but is lower than the third year rates reported by the other centres. The percentage of interval cancers developing in women who had undergone assessment was slightly lower than the Scottish figure of 16%.2 However, after exclusion of cancers arising at a different location or in the opposite breast, the number of interval cancers following false negative assessment in this study was only 16 (6%) from a total of 256 cases. Although this number is reassuringly small, efforts should continue to refine the assessment process so that more small and subtle cancers maybe detected through screening. Measures have already been taken by the NHSBSP to reduce the number of interval cancers developing after initial screening. All Units are required to achieve the optimum mammographic film density of 1.4–1.8.4 All women attending for their first screen have two view mammograms taken as this has been shown to increased the cancer detection rate by 24% compared to single view mammography.10 Double
a) 18 mm poorly defined mass b) No change No change in mammographic appearance No change – mammograms and ultrasound reported as normal No change in mammographic appearance None taken – palpable carcinoma at same site as screening abnormality Diffuse asymmetry/inflammatory carcinoma No change in mammographic appearance No change in mammographic appearance No change in mammographic appearance More prominent asymmetry Ultrasound imaged a 16 mm solid mass 30 mm mass with in part a well defined, but in part an irregular margin No change in mammographic appearance 21 mm mass seen with untrasound No change in mammographic appearance RT – 18 mm poorly defined mass LT – Mass decreased in size No change in mammographic appearance Ultrasound imaged a solid mass 18 mm irregular mass + clacification
reporting of films is adopted by 76% of Units11 in the UK as it is reported to increase the sensitivity of cancer detection by up to 13%.12,13 Most films were single read between 1991 and 1993, but since 1994 the Leeds Wakefield Breast Screening Service has operated a policy of double reading with third reader arbitration. This is only possible as the unit is large, screening a population of 86,000 women aged 50–64 years, and employing five radiologists. Single reading is still unavoidable at times of radiologists’ absence. This film reading practice14 has been shown to result in increased detection of small invasive cancers without a rise in the recall to assessment rate for apparent abnormalities that prove to be insignificant. As the NHS Breast Screening Programme has evolved, each unit has developed their own assessment protocols based on local audit and dissemination of best practice through journals, education meetings and the quality assurance process. There is, however, a great diversity of models for further assessment of screen-detected abnormalities.15 Are there lessons to learn from this detailed review of the Leeds Wakefield interval cancer cases? In common with the Scottish study2 most of the false negative cases did not undergo needle biopsy. Between 1991 and 1994, 12 cases were assessed but only 2 underwent FNAC as part of the assessment process. Since 1995, 3 of 4 cases underwent needle biopsy. Eight cases were recalled for assessment of a mass/masses. Most were thought to be radiologically benign, but in cases 3 and 8 the masses were noted to be
Are too many breast cancers missed at assessment? 205
Fig. 1
Case 14 – Screening mammograms (1995). Recalled for assessment of similar looking masses (Rt & LT).
Fig. 2 Case 14 – Ultrasound (1995) of screen detected masses which looked ultrasonically identical. Misinterpreted as representing bilateral cysts. No FNACs performed.
206
The Breast
Fig. 3 Case 14 – Symptomatic mammograms (1997). The Rt breast mass has increased in size and proved to represent a palpable carcinoma. The Lt breast mass is smaller.
radiologically suspicious or indeterminate. As no change was observed compared to symptomatic mammograms taken two years previously, no further action was taken. Ultrasound imaged solid masses in 5 cases and cysts in 2 cases, none of which were aspirated. In case 6, solid/cystic differentiation of the small mass was not possible. Cases 11 and 13 may be regarded as unfortunate and a failure of cytology, possibly due to inaccurate tissue sampling. Both underwent ultrasound guided fine needle aspiration cytology which was reported as benign. Retrospective review of case 13 raised doubt as to whether the mass seen on ultrasound did in fact represent the mammographic mass which was situated posteriorly in the breast and was not accessible to stereotactic biopsy. However, it is reasonable to suggest that the other cases may have been diagnosed earlier if FNAC or core biopsy had been performed. Image guided needle biopsy is now included in the Leeds Wakefield Assessment Protocol for the assessment of all solid masses as well as of small masses where cystic/solid differentiation
is uncertain. However, difficulties may still arise in cases of multiple solid masses or in the assessment of masses in difficult locations, particularly those located posteriorly in the breast which are not visualized on ultrasound. In cases 2 and 8, two separate but similar looking masses were assessed and in each case one of the masses in each patient proved to be a carcinoma and the other a fibroadenoma. Six cases were recalled for assessment of possible stromal deformity which in all except case 7 was thought to represent composite shadowing following further mammographic views. There was palpable thickening in three cases, and a palpable lump thought on ultrasound to represent a cyst in the other. Fine needle aspiration cytology was performed in only cases 7 and 15, and was image guided in the former. It is now our policy to perform image guided core biopsy from all areas of stromal deformity persisting on focal compression views and when there is palpable thickening corresponding in position with an area of possible stromal deformity, even if it is thought to represent composite shadowing.
Are too many breast cancers missed at assessment? 207 Case 16 was assessed for a small cluster of radiologically indeterminate calcification, but was returned to routine recall after a benign stereotactic guided core biopsy containing pathological calcification was obtained. It was not our practice to X-ray the cores in 1996, but now all are X-rayed to ascertain if they contain calcification representative of that seen on the mammogram. In summary, some cancers may have been detected earlier if image guided needle biopsy had been included in the assessment of a) all solid masses and complex cysts including those where cystic/solid differentiation was uncertain; b) radiologically suspicious abnormalities even if they remained unchanged in appearance from previous films; and c) areas of stromal deformity thought to be composite if there was associated palpable thickening. Although interval cancers arising after false negative assessment accounted for only 6% of the total number at the Leeds Wakefield Screening Service, data from other units should be collected for comparison. Guidelines from the NHS Brease Screening Programme are awaited to ensure uniformity of the assessment process throughout the UK. The exciting challenge facing all breast screening radiologists is to extend the boundaries so that even subtler breast cancers are detected as early as possible. We should constantly seek to improve the screening assessment process to achieve the highest possible small invasive cancer detection rates whilst maintaining a low surgical biopsy rate for abnormalities that prove to be benign.
Acknowledgement I would like to thank the Yorkshire Breast Screening Quality Assurance Reference Centre and Cancer Registry, without whose help this data could not have been collected.
References 1. Field S. Breast screening issues. Newsletter of Royal College of Radiologists 1998; 54: 12–14. 2. Everington D, Gilbert F, Tyack C et al. The Scottish breast screening programme’s experience of monitoring interval cancers. J Med Screen 1999; 6: 21–27. 3. Patrick J, Muir Gray J. Guidelines on the collection and use of breast cancer data. NHSBSP Publication No. 26, 1993. 4. Quality Assurance Guidelines for Radiologists. NHSBSP Publication No. 15, May 1997. 5. Moss S, Blanks R for the Interval Cancer Working Group. Calculating appropriate target cancer detection rates and expected interval cancer rates for the UK NHS Breast Screening Programme. J Epidermiol Community Health 1998; 52: 111–115. 6. Peeters P, Verbeek K, Hendricks J et al. The occurrence of interval cancers in the Nijmegan Screening Programme. Br J Cancer 1989; 59: 929–932. 7. Woodman C B J, Threlfall A, Boggis C R M et al. Is the three year breast screening interval too long? Occurrence of interval cancers in the NHS Breast Screening Programme’s North Western Region. BMJ 1995; 310: 224–226. 8. Day N, McCann J, Camilleri-Ferrante C et al. Monitoring interval cancers in breast screening programmes: the East Anglian experience. J Med Screen 1995; 2: 180–185. 9. Liston J. A review of Yorkshire Interval Breast Cancers. Yorkshire Oncology Newsletter. Spring 1996; 14–16. 10. Wald N J, Murphy P, Major P et al. UK CCCR Multicentre randomised controlled trial of one and two view mammography in breast screening. BMJ 1995; 311: 1189–1193. 11. Wells J, Cooke J. Film reading practice of UK breast screening units. The Breast 1996; 5: 404–409. 12. Anderson E D C, Muir B B, Walsh J S et al. The efficacy of double reading mammograms in breast screening. Clin Radiol 1994; 49: 248–2251. 13. Deans H E, Everington D, Cordiner C et al. Scottish experience of double reading in the National Breast Screening Programme. The Breast 1998; 7: 75–79. 14. Blanks R, Wallis M, Moss S. A comparison of cancer detection rates achieved by breast cancer screening programmes by number of readers, for one and two view mammography: results from the UK NHS Breast Screening Programme. J Med Screen 1998; 5: 195–201. 15. Gerard K, Brown J, Johnston K et al. The UK Breast Screening Programme: Local service organisation and delivery. HERG Discussion paper No. 15, October 1996.
ORIGINAL ARTICLE
Are too many breast cancers missed at assessment? J. Liston Leeds Wakefield Breast Screening Service, Seacroft Hospital, Leeds, UK. S U M M A R Y. Interval breast cancers presenting between screening episodes are an inevitable occurrence but their number should to be kept to a minimum. The objectives of this study were to ascertain the proportion of interval cancers developing in women who had been recalled for assessment after their initial screen and to review the assessment process. Interval cancers presenting after false negative assessment accounted for a small proportion (6%) but some cancers may have been diagnosed earlier if image guided FNAC or core biopsy had been included in the assessment process. © 2000 Harcourt Publishers Ltd
INTRODUCTION
to be surprisingly high, although it was not known whether the cancer had been incorrectly assessed or whether the woman had been recalled for a different lesion. This retrospective study was undertaken to ascertain the magnitude of the problem at the Leeds Wakefield Breast Screening Service.
Interval breast cancers, defined as cancers arising less than 36 months after a negative screening mammogram are an expected and unavoidable occurrence within a screening programme, but their numbers need to be kept as low as possible if mortality reductions in the screened population are to be achieved. The aim of NHS Breast Screening Programme as given in ‘Health of the Nation’ (Secretary of State for Health 1992) is to reduce mortality from breast cancer amongst women in the screening age group by 25%. Minimising the number of interval cancers should also reduce the risk of litigation. A survey conducted by Professor Field1 reported that 27% of screening units in the UK had been involved in litigation at some time. Approximately half of the cases were current and most arose due to cancers in whom the diagnosis had been delayed. Unrealistic public expectation fuelled by the press is partly to blame, but society as a whole is becoming increasingly litigious. Published papers have documented the number of interval cancers arising at different time intervals after screening, but there are few published data on the number of women who have attended for further assessment before being reassured that breast cancer has been excluded. The Scottish Breast Screening Programme recently published data2 stating that 16% of women who developed an interval cancer had attended an assessment clinic. The number was thought
METHOD Accurate and timely ascertainment of interval cancer data is acknowledged to be difficult. In the Yorkshire part of the Northern & Yorkshire region we are fortunate to have systematic sharing of information between the Northern & Yorkshire Cancer Registry Information Service (formally the Yorkshire Cancer Registry) and the Quality Assurance Reference Centre for Breast Screening. The Cancer Registry informs an officer from the Quality Assurance Reference Centre of all newly registered cases of breast cancer. The details are manually correlated with data held at each of the four screening units and each case classified as either a screen detected cancer, interval cancer, cancer in a lapsed attender, cancer in a non-attender, or cancer in a woman who has not been invited for screening in accordance with the NHSBSP guidelines on the collection and use of breast cancer data.3 Ascertainment of interval cancer cases developing up to three years after a negative screen is thought to be complete for women screened between January 1991 and March 1995. The Yorkshire breast screening radiologists meet every three months to review and classify interval cancer cases by
Address correspondence to: Dr J Liston MBBS, FRCR, Leeds Wakefield Breast Screening Service, Seacroft Hospital, Leeds LS14 6UH, UK. Tel.: 0113 206 3769; Fax: 0113 206 3796
201
202
The Breast
the method outlined in the NHSBSP Quality Assurance Guidelines for Radiologists.4 All interval cancer cases known to the Leeds Wakefield Breast Screening Service on 21 December 1998 were retrospectively reviewed to ascertain if they had attended an assessment clinic, and if so a detailed analysis was made of the tests performed.
RESULTS Table 1 shows the number of interval cancers and the rate per 10,000 women screened with 95% confidence intervals by screening year cohort for the periods up to 12, 24 and 36 months since the last negative screen. To date, a total of 256 intervals cancers have been identified in the 144,208 women screened between 1991 and 31 March 1998. The number of interval cancers registered within one, two and three years of screening were 66, 95, and 95 respectively, although these numbers will increase with further follow-up. Table 1 also shows the invasive cancer detection rates. Between 1991 and 31 March 1998, 730 breast cancers were screen detected, 585 of which were invasive cancers. Ascertainment of interval cancer data (< 24 months) is thought to be complete for all women screened up until March 1996, with complete three year data for women screened prior to April 1995. The rate of interval cancers presenting within two years of a negative screen is 14.2/10,000 screened and the rate presenting in the third year after a negative screen is 12.0/10,000 screened. Interval cancers developing in women who had been recalled for further assessment after screening accounted for 31 (12%) of the 256 cases. Further analysis found that 7 of the women had been recalled for further assessment of their
contralateral breast, and 8 women because of an apparent abnormality in the same breast in which a cancer subsequently developed, but at a different site. The remaining 16 (6%) women had been recalled for assessment of an abnormality which subsequently grew and presented symptomatically as an interval cancer. This small group of women had undergone false negative assessment and been falsely reassured. Details of the procedures undertaken at the assessment clinic are given in Table 2. The women ranged in age from 49–63 years (mean 56 years) when their initial screen was undertaken. Eight were recalled for assessment of a mass(es), 6 for possible stromal deformity and one for calcification. One woman was recalled as she told the radiographers that she could feel a lump in her breast. Ultrasound was performed in all except the calcification case and one of the cases of stromal deformity. All women were clinically examined – 10 had no palpable abnormality, 5 had a focal area of palpable thickening and one a palpable lump thought to be benign. Assessment included needle biopsy (FNAC or core biopsy) in only 5 women. Table 3 documents the time between screening and development of the interval cancer and gives pathological details. The interval ranged between 4 and 32 months (mean 15 months). All cases except one presented symptomatically with either a palpable lump or distortion. The other was detected on a mammogram taken as part of a family history screen. The cancers were of varied type and ranged in size from 4–38 mm (mean 16 mm). Nine were node negative, 4 were node positive but with less than 4 nodes involved. The node status was unknown in 3 cases including case 7 who presented with clinically advanced carcinoma which was treated with primary chemotherapy.
Table 1 Numbers of interval cancers, rate per 10,000 women screened, and 95% confidence intervals for the periods up to 12, 24 and 36 months since the last negative screen. The invasive cancer detection rate per 10,000 women is also given Screening year
Number of women screened
Invasive cancer detection rate per 10,000
Number of interval cancers Rate per 10,000 women screened (95% CI) 0 – < 12 months 12 – < 24 months – – 7 4.4 11 5.3 14 6.5 14 7.4 7 3.6 4 2.0 8*
1990–91
1364
36
1991–92
15,970
32
1992–93
20,559
38
1993–94
21,635
41
1994–95
18,833
36
1995–96
19,684
39
1996–97
19,948
41
1997–98
26,215
*Ascertainment incomplete.
51
(1.7 to 9.0) (2.7 to 9.6) (3.5 to 10.8) (4.1 to 12.5) (1.4 to 7.3) (0.5 to 5.1)
2 14.6 18 11.2 (6.6 to 17.8) 15 7.3 (4.1 to 12.0) 22 10.2 (6.4 to 15.4) 16 8.5 (4.8 to 13.8) 14 7.1 (3.9 to 11.9) 8*
24 – < 36 months 2 14.6 16 10.0 (5.7 to 16.2) 30 14.6 (9.8 to 20.8) 24 11.1 (7.1 to 16.5) 12 6.4 (3.3 to 11.1) 10* 1*
Are too many breast cancers missed at assessment? 203 Table 2 Case
Tests undertaken at assessment Age when screened
Date of assessment
Mammogram report
Ultrasound report
Clinical examination
FNAC/core biopsy
1 2
61 56
9/91 4/92
– –
50
8/92
Normal
–
4
49
3/93
Thickening
–
5
63
2/93
?Stromal Deformity → composite (RN) Normal (RN)
Cyst Solid masses 3 2 Solid mass ?intramammary lymph node Normal
Normal Normal
3
10 mm Mass (RB) 15 mm + 10 mm masses (RB) 15 mm mass (RS) but unchanged in 2 years
Normal
–
6
56
6/93
14 mm mas (RU)
Thickening (bilateral) Normal
7
61
6/93
Normal
C2 (stereo guided)
8
53
8/93
Solid masses 32
Normal
–
9
59
2/94
–
Normal
–
10
53
3/94
9 mm cyst
Palpable lump (PB)
–
11 12
53 53
5/94 10/94
Solid mass Normal
Thickening Thickening
C2 (u/s guided) –
13
56
2/95
?Stromal deformity (RU) 12 mm masses (RB + RU) but unchanged in 2 years ?Stromal Deformity → composite (RN) Asymmetry + ?Stromal deformity → composite (RB) 10 mm mass (RB) ?Stromal deformity → composite (RN) 10 mm Mass (RB)
Normal
C2 with lymphoid cells (u/s guided)
14 15
50 60
11/95 6/96
Solid mass ?Intramammary lymph node Cysts Area of benign breast change
Normal Thickening
– C3 + C2 (clinical)
16
59
7/96
–
Normal
B2 (stereo guided)
Bilateral masses (RB) Asymmetry + ?Stromal deformity → composite (RB) New calcification (RU)
Cyst with low level echoes Normal
–
RN/RB/RU/RS = Radiologically normal/benign/uncertain/suspicious.
Table 3
Pathology of interval cancers
Case
Interval (Months)
Pathology
Lymph Node Status
1 2 3 4 5 6 7 8* 9* 10 11 12 13 14 15* 16
15 32 11 25 6 16 16 13 14 10 14 12 4 17 12 28
38 mm Primary Breast Sarcoma 20 mm NST (II) + fibroadenoma 14 mm NST (II) 20 mm lobular Ca 12 mm NST (II) 15 mm NST (grade unknown) Rx Primary chemotherapy 15 mm NST (I) + fibroadenoma 4 mm NST/Tubular (II) 7 mm NST (II) 14 mm Intracystic papillary Ca + 2 mm NST (I) 15 mm Tubular Ca 10 mm Mucinous Ca (I) 20 mm NST (III) 18 mm NST (I) 22 mm NST (II)
0/13 0/13 – 0/7 0/14 2/5 – 0/22 0/21 – 1/9 1/6 0/2 0/7 3/9 0/9
*Wire guided.
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Table 4
Comparison of screening/assessment imaging with imaging performed at the time of symptomatic presentation – a retrospective review
Case
Screening/Assessment Imaging
Symptomatic Imaging 50 mm poorly defined mass
11
10 mm mass with unclear margins thought to represent a ‘cyst’ with ultrasound a) 10 mm solid mass with unclear margins b) 15 mm solid mass with unclear margins 15 mm solid mass with irregular margins unchanged over 2 years Possible stromal deformity/normal ultrasound 15 mm ill-defined asymmetry 14 mm mass with unclear margins thought to represent a ‘cyst’ with ultrasound Possible stromal deformity a) 12 mm solid mass with unclear margins b) 12 mm solid mass with well defined margines 10 mm area of asymmetry + possible distortion Asymmetry + possible stromal deformity 9 mm ‘cyst’ imaged with ultrasound 10 mm well-defined solid mass
12
Possible stromal deformity/normal ultrasound
13 14
10 mm well-defined solid mass RT – 10 mm mass with unclear margins thought to represent a ‘cyst’ with ultrasound LT – 8 mm mass with unclear margins thought to represent a ‘cyst’ with ultrasound 30 mm irregular asymmetry + possible distortion Ultrasound imaged benign breast change only Small cluster of new calcification
1 2 3 4 5 6 7 8 9 10
15 16
DISCUSSION The number of interval cancers presenting within the first two years of a negative screen at the Leeds Wakefield Breast Screening Service exceeds the NHSBSP4,5 expected rate of less than 12.0/10,000 screened, but are comparable with other UK and European published data – Nijmegen,6 North West Region,7 East Anglia,8 Yorkshire9 and the recent Scottish data.2 The third year rate is comparable to the Yorkshire and Scottish data but is lower than the third year rates reported by the other centres. The percentage of interval cancers developing in women who had undergone assessment was slightly lower than the Scottish figure of 16%.2 However, after exclusion of cancers arising at a different location or in the opposite breast, the number of interval cancers following false negative assessment in this study was only 16 (6%) from a total of 256 cases. Although this number is reassuringly small, efforts should continue to refine the assessment process so that more small and subtle cancers maybe detected through screening. Measures have already been taken by the NHSBSP to reduce the number of interval cancers developing after initial screening. All Units are required to achieve the optimum mammographic film density of 1.4–1.8.4 All women attending for their first screen have two view mammograms taken as this has been shown to increased the cancer detection rate by 24% compared to single view mammography.10 Double
a) 18 mm poorly defined mass b) No change No change in mammographic appearance No change – mammograms and ultrasound reported as normal No change in mammographic appearance None taken – palpable carcinoma at same site as screening abnormality Diffuse asymmetry/inflammatory carcinoma No change in mammographic appearance No change in mammographic appearance No change in mammographic appearance More prominent asymmetry Ultrasound imaged a 16 mm solid mass 30 mm mass with in part a well defined, but in part an irregular margin No change in mammographic appearance 21 mm mass seen with untrasound No change in mammographic appearance RT – 18 mm poorly defined mass LT – Mass decreased in size No change in mammographic appearance Ultrasound imaged a solid mass 18 mm irregular mass + clacification
reporting of films is adopted by 76% of Units11 in the UK as it is reported to increase the sensitivity of cancer detection by up to 13%.12,13 Most films were single read between 1991 and 1993, but since 1994 the Leeds Wakefield Breast Screening Service has operated a policy of double reading with third reader arbitration. This is only possible as the unit is large, screening a population of 86,000 women aged 50–64 years, and employing five radiologists. Single reading is still unavoidable at times of radiologists’ absence. This film reading practice14 has been shown to result in increased detection of small invasive cancers without a rise in the recall to assessment rate for apparent abnormalities that prove to be insignificant. As the NHS Breast Screening Programme has evolved, each unit has developed their own assessment protocols based on local audit and dissemination of best practice through journals, education meetings and the quality assurance process. There is, however, a great diversity of models for further assessment of screen-detected abnormalities.15 Are there lessons to learn from this detailed review of the Leeds Wakefield interval cancer cases? In common with the Scottish study2 most of the false negative cases did not undergo needle biopsy. Between 1991 and 1994, 12 cases were assessed but only 2 underwent FNAC as part of the assessment process. Since 1995, 3 of 4 cases underwent needle biopsy. Eight cases were recalled for assessment of a mass/masses. Most were thought to be radiologically benign, but in cases 3 and 8 the masses were noted to be
Are too many breast cancers missed at assessment? 205
Fig. 1
Case 14 – Screening mammograms (1995). Recalled for assessment of similar looking masses (Rt & LT).
Fig. 2 Case 14 – Ultrasound (1995) of screen detected masses which looked ultrasonically identical. Misinterpreted as representing bilateral cysts. No FNACs performed.
206
The Breast
Fig. 3 Case 14 – Symptomatic mammograms (1997). The Rt breast mass has increased in size and proved to represent a palpable carcinoma. The Lt breast mass is smaller.
radiologically suspicious or indeterminate. As no change was observed compared to symptomatic mammograms taken two years previously, no further action was taken. Ultrasound imaged solid masses in 5 cases and cysts in 2 cases, none of which were aspirated. In case 6, solid/cystic differentiation of the small mass was not possible. Cases 11 and 13 may be regarded as unfortunate and a failure of cytology, possibly due to inaccurate tissue sampling. Both underwent ultrasound guided fine needle aspiration cytology which was reported as benign. Retrospective review of case 13 raised doubt as to whether the mass seen on ultrasound did in fact represent the mammographic mass which was situated posteriorly in the breast and was not accessible to stereotactic biopsy. However, it is reasonable to suggest that the other cases may have been diagnosed earlier if FNAC or core biopsy had been performed. Image guided needle biopsy is now included in the Leeds Wakefield Assessment Protocol for the assessment of all solid masses as well as of small masses where cystic/solid differentiation
is uncertain. However, difficulties may still arise in cases of multiple solid masses or in the assessment of masses in difficult locations, particularly those located posteriorly in the breast which are not visualized on ultrasound. In cases 2 and 8, two separate but similar looking masses were assessed and in each case one of the masses in each patient proved to be a carcinoma and the other a fibroadenoma. Six cases were recalled for assessment of possible stromal deformity which in all except case 7 was thought to represent composite shadowing following further mammographic views. There was palpable thickening in three cases, and a palpable lump thought on ultrasound to represent a cyst in the other. Fine needle aspiration cytology was performed in only cases 7 and 15, and was image guided in the former. It is now our policy to perform image guided core biopsy from all areas of stromal deformity persisting on focal compression views and when there is palpable thickening corresponding in position with an area of possible stromal deformity, even if it is thought to represent composite shadowing.
Are too many breast cancers missed at assessment? 207 Case 16 was assessed for a small cluster of radiologically indeterminate calcification, but was returned to routine recall after a benign stereotactic guided core biopsy containing pathological calcification was obtained. It was not our practice to X-ray the cores in 1996, but now all are X-rayed to ascertain if they contain calcification representative of that seen on the mammogram. In summary, some cancers may have been detected earlier if image guided needle biopsy had been included in the assessment of a) all solid masses and complex cysts including those where cystic/solid differentiation was uncertain; b) radiologically suspicious abnormalities even if they remained unchanged in appearance from previous films; and c) areas of stromal deformity thought to be composite if there was associated palpable thickening. Although interval cancers arising after false negative assessment accounted for only 6% of the total number at the Leeds Wakefield Screening Service, data from other units should be collected for comparison. Guidelines from the NHS Brease Screening Programme are awaited to ensure uniformity of the assessment process throughout the UK. The exciting challenge facing all breast screening radiologists is to extend the boundaries so that even subtler breast cancers are detected as early as possible. We should constantly seek to improve the screening assessment process to achieve the highest possible small invasive cancer detection rates whilst maintaining a low surgical biopsy rate for abnormalities that prove to be benign.
Acknowledgement I would like to thank the Yorkshire Breast Screening Quality Assurance Reference Centre and Cancer Registry, without whose help this data could not have been collected.
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